Oxygen-substituted 3-heteroaroylamino-propionic acid derivatives and their use as pharmaceuticals

ABSTRACT

The present invention relates to compounds of the formula I, wherein A, D, E, G, R 10 , R 30 , R 40 , R 50  and R 60  have the meanings indicated in the claims, which are valuable pharmaceutical active compounds. They are inhibitors of the protease cathepsin A, and are useful for the treatment of diseases such as atherosclerosis, heart failure, renal diseases, liver diseases or inflammatory diseases, for example. The invention furthermore relates to processes for the preparation of the compounds of the formula I, their use and pharmaceutical compositions comprising them.

The present invention relates to compounds of the formula I,

wherein A, D, E, G, R¹⁰, R³⁰, R⁴⁰, R⁵⁰ and R⁶⁰ have the meaningsindicated below, which are valuable pharmaceutical active compounds.They are inhibitors of the protease cathepsin A, and are useful for thetreatment of diseases such as atherosclerosis, heart failure, renaldiseases, liver diseases or inflammatory diseases, for example. Theinvention furthermore relates to processes for the preparation of thecompounds of the formula I, their use and pharmaceutical compositionscomprising them.

Cathepsin A (EC=3.4.16.5; gene symbol CTSA) is a protease also known aslysosomal carboxypeptidase A or protective protein. It belongs to afamily of serine carboxypeptidases which contains only two othermammalian representatives, retinoid-inducible serine carboxypeptidaseand vitellogenic carboxypeptidase-like protein. Within the cellcathepsin A resides in lysosomes where it forms a high molecular weightcomplex with beta-galactosidase and neuraminidase. The interaction ofcathepsin A with these glycosidases is essential for their correctrouting to the lysosome and protects them from intralysosomalproteolysis. A deficiency of cathepsin A resulting from variousmutations in the ctsa gene leads to a secondary deficiency ofbeta-galactosidase and neuraminidase that is manifest as the autosomalrecessive lysosomal storage disorder galactosialidosis (cf. A. d'Azzo etal., in “The Metabolic and Molecular Bases of Inherited Disease”, vol. 2(1995), 2835-2837). The majority of identified mutations in ctsa aremissense mutations affecting the folding or the stability of theprotein. None of them was shown to occur in the active site of theenzyme (G. Rudenko et al., Proc. Natl. Acad. Sci. USA 95 (1998),621-625). Accordingly, the lysosomal storage disorder can be correctedwith catalytically inactive cathepsin A mutants (N. J. Galjart et al.,J. Biol. Chem. 266 (1991), 14754-14762). The structural function ofcathepsin A is therefore separable from its catalytic activity. This isalso underscored by the observation that in contrast to mice deficientin the ctsa gene, mice carrying a catalytically inactivating mutation inthe ctsa gene do not develop signs of the human diseasegalactosialidosis (R. J. Rottier et al., Hum. Mol. Genet. 7 (1998),1787-1794; V. Seyrantepe et al., Circulation 117 (2008), 1973-1981).

Cathepsin A displays carboxypeptidase activity at acidic pH anddeamidase and esterase activities at neutral pH against variousnaturally occurring bioactive peptides. In vitro studies have indicatedthat cathepsin A converts angiotensin I to angiotensin 1-9 andbradykinin to bradykinin 1-8, which is the ligand for the bradykinin B1receptor. It hydrolyzes endothelin-1, neurokinin and oxytocin, anddeamidates substance P (cf. M. Hiraiwa, Cell. Mol. Life Sci. 56 (1999),894-907). High cathepsin A activity has been detected in urine,suggesting that it is responsible for tubular bradykinin degradation (M.Saito et al., Int. J. Tiss. Reac. 17 (1995), 181-190). However, theenzyme can also be released from platelets and lymphocytes and isexpressed in antigen-presenting cells where it might be involved inantigen processing (W. L. Hanna et al., J. Immunol. 153 (1994),4663-4672; H. Ostrowska, Thromb. Res. 86 (1997), 393-404; M. Reich etal., Immunol. Lett. (online Nov. 30, 2009)). Immunohistochemistry ofhuman organs revealed prominent expression in renal tubular cells,bronchial epithelial cells, Leydig's cells of the testis and largeneurons of the brain (O. Sohma et al., Pediatr. Neurol. 20 (1999),210-214). It is upregulated during differentiation of monocytes tomacrophages (N. M. Stamatos et al., FEBS J. 272 (2005), 2545-2556).Apart from structural and enzymatic functions, cathepsin A has beenshown to associate with neuraminidase and an alternatively splicedbeta-galactosidase to form the cell-surface laminin and elastin receptorcomplex expressed on fibroblasts, smooth muscle cells, chondroblasts,leukocytes and certain cancer cell types (A. Hinek, Biol. Chem. 377(1996), 471-480).

The importance of cathepsin A for the regulation of local bradykininlevels has been demonstrated in animal models of hypertension.Pharmacological inhibition of cathepsin A activity increased renalbradykinin levels and prevented the development of salt-inducedhypertension (H. Ito et al., Br. J. Pharmacol. 126 (1999), 613-620).This could also be achieved by antisense oligonucleotides suppressingthe expression of cathepsin A (I. Hajashi et al., Br. J. Pharmacol. 131(2000), 820-826). Besides in hypertension, beneficial effects ofbradykinin have been demonstrated in various further cardiovasculardiseases and other diseases (cf. J. Chao et al., Biol. Chem. 387 (2006),665-75; P. Madeddu et al., Nat. Clin. Pract. Nephrol. 3 (2007),208-221). Key indications of cathepsin A inhibitors therefore includeatherosclerosis, heart failure, cardiac infarction, cardiac hypertrophy,vascular hypertrophy, left ventricular dysfunction, in particular leftventricular dysfunction after myocardial infarction, renal diseases suchas renal fibrosis, renal failure and kidney insufficiency; liverdiseases such as liver fibrosis and liver cirrhosis, diabetescomplications such as nephropathy, as well as organ protection of organssuch as the heart and the kidney.

As indicated above, cathepsin A inhibitors can prevent the generation ofthe bradykinin B1 receptor ligand bradykinin 1-8 (M. Saito et al., Int.J. Tiss. Reac. 17 (1995), 181-190). This offers the opportunity to usecathepsin A inhibitors for the treatment of pain, in particularneuropathic pain, and inflammation, as has been shown for bradykinin B1receptor antagonists (cf. F. Marceau et al., Nat. Rev. Drug Discov. 3(2004), 845-852). Cathepsin A inhibitors can further be used asanti-platelet agents as has been demonstrated for the cathepsin Ainhibitor ebelactone B, a propiolactone derivative, which suppressesplatelet aggregation in hypertensive animals (H. Ostrowska et al., J.Cardiovasc. Pharmacol. 45 (2005), 348-353).

Further, like other serine proteases such as prostasin, elastase ormatriptase, cathepsin A can stimulate the amiloride-sensitive epithelialsodium channel (ENaC) and is thereby involved in the regulation of fluidvolumes across epithelial membranes (cf. C. Planes et al., Curr. Top.Dev. Biol. 78 (2007), 23-46). Thus, respiratory diseases can beameliorated by the use of cathepsin A inhibitors, such as cysticfibrosis, chronic bronchitis, chronic obstructive pulmonary disease,asthma, respiratory tract infections and lung carcinoma. Cathepsin Amodulation in the kidney could be used to promote diuresis and therebyinduce a hypotensive effect.

Besides for the above-mentioned compound ebelactone B, an inhibitoryeffect on cathepsin A has been found for certain dipeptidicphenylalanine derivatives which are described in JP 2005/145839. Thereis a need for further compounds which inhibit cathepsin A and offer anopportunity for the treatment of the mentioned diseases and furtherdiseases in which cathepsin A plays a role. The present inventionsatisfies this need by providing the oxygen-substituted3-heteroaroylamino-propionic acid derivatives of the formula I definedbelow.

Certain compounds in which a 3-heteroaroylamino-propionic acid moietycan be present, have already been described. For example, in WO2006/076202 amine derivatives, which modulate the activity of steroidnuclear receptors, are described which carry on the nitrogen atom of theamine function a heteroaroyl group and a further group which is definedvery broadly. In US 2004/0072802 broadly-defined beta-amino acidderivatives are described which carry an acyl group on the beta-aminogroup and are inhibitors of matrix metalloproteases and/or tumornecrosis factor. In WO 2009/080226 and WO 2009/080227, which relate toantagonists of the platelet ADP receptor P2Y12 and inhibit plateletaggregation, pyrazoloylamino-substituted carboxylic acid derivatives aredescribed which, however, additionally carry a carboxylic acidderivative group on the carbon atom carrying the pyrazoloylamino group.Other pyrazoloylamino-substituted compounds, in which the nitrogen atomof the amino group is connected to a ring system and which areinhibitors of the blood clotting enzymes factor Xa and/or factor VIIa,are described in WO 2004/056815.

A subject of the present invention is a compound of the formula I, inany of its stereoisomeric forms or a mixture of stereoisomeric forms inany ratio, or a physiologically acceptable salt thereof, or aphysiologically acceptable solvate of any of them,

wherein

-   A is chosen from the series consisting of C(R¹) and N;-   D is chosen from the series consisting of N(R²), O and S;-   E is chosen from the series consisting of C(R³) and N;-   G is chosen from the series consisting of R⁷¹—O—C(O)—,    R⁷²—N(R⁷³)—C(O)—, NC— and tetrazol-5-yl;-   R¹ is chosen from the series consisting of hydrogen, halogen,    (C₁-C₆)-alkyl, Ar, HO—, (C₁-C₆)-alkyl-O—, (C₁-C₆)-alkyl-S(O)_(m)—    and NC—;-   R² is chosen from the series consisting of (C₁-C₇)-alkyl,    (C₃-C₇)-cycloalkyl-C_(s)H_(2s)— and Ar—C_(s)H_(2s)—, wherein s is an    integer chosen from the series consisting of 0, 1, 2 and 3;-   R³ is chosen from the series consisting of hydrogen, halogen,    (C₁-C₆)-alkyl, (C₁-C₆)-alkyl-O—, (C₁-C₆)-alkyl-S(O)_(m)— and NC—;-   R¹⁰ is chosen from the series consisting of R¹¹—O—,    R¹²—N(R¹³)—C(O)—O— and Het²—C(O)—O—;-   R¹¹ is chosen from the series consisting of hydrogen, R¹⁴,    (C₃-C₇)-cycloalkyl, Ar and Het³;-   R¹² and R¹³ are independently of each other chosen from the series    consisting of hydrogen, R¹⁵ and Ar;-   R¹⁴ is (C₁-C₁₀)-alkyl which is optionally substituted by one or more    identical or different substituents chosen from the series    consisting of halogen, HO—, R¹⁶—O—, oxo, (C₃-C₇)-cycloalkyl, Ar,    Het¹, Het³, NC—, H₂N—C(O)—, (C₁-C₄)-alkyl-NH—C(O)—,    di((C₁-C₄)-alkyl)N—C(O)—, Het¹—C(O)—, (C₁-C₄)-alkyl-C(O)—NH— and    (C₁-C₄)-alkyl-S(O)_(m)—;-   R¹⁵ is (C₁-C₆)-alkyl which is optionally substituted by one or more    identical or different substituents chosen from the series    consisting halogen, HO— and (C₁-C₆)-alkyl-O—;-   R¹⁶ is (C₁-C₆)-alkyl which is optionally substituted by one or more    identical or different substituents chosen from the series    consisting of HO—, (C₁-C₄)-alkyl-O— and NC—;-   R³⁰ is chosen from the series consisting of R³¹, (C₃-C₇)-cycloalkyl,    R³²—C_(u)H_(2u)— and Het³—C_(u)H_(2u)—, wherein u is an integer    chosen from the series consisting of 0, 1, 2 and 3;-   R³¹ is (C₁-C₁₀)-alkyl which is optionally substituted by one or more    identical or different substituents chosen from the series    consisting of halogen, (C₃-C₇)-cycloalkyl, HO—, (C₁-C₆)-alkyl-O—,    (C₁-C₆)-alkyl-S(O)_(m)— and NC—;-   R³² is chosen from the series consisting of phenyl and an aromatic    5-membered or 6-membered monocyclic heterocycle which comprises one,    two or three identical or different ring heteroatoms chosen from the    series consisting of nitrogen, oxygen and sulfur and is bonded via a    ring carbon atom, wherein the phenyl and the heterocycle all are    optionally substituted by one or more identical or different    substituents chosen from the series consisting of halogen,    (C₁-C₆)-alkyl, (C₃-C₇)-cycloalkyl, R³³, HO—, (C₁-C₆)-alkyl-O—,    R³³—O—, R³³—(C₁-C₄)-alkyl-O—, —O—CH₂—O—, —O—CF₂—O—,    (C₁-C₆)-alkyl-S(O)_(m)—, H₂N—S(O)₂—, (C₁-C₄)-alkyl-NH—S(O)₂—,    di((C₁-C₄)-alkyl)N—S(O)₂—, H₂N—, (C₁-C₆)-alkyl-NH—,    di((C₁-C₆)-alkyl)N—, Het¹, (C₁-C₄)-alkyl-C(O)—NH—, Ar—C(O)—NH—,    (C₁-C₄)-alkyl-S(O)₂—NH— and NC—;-   R³³ is chosen from the series consisting of phenyl and an aromatic    5-membered or 6-membered monocyclic heterocycle which comprises one,    two or three identical or different ring heteroatoms chosen from the    series consisting of nitrogen, oxygen and sulfur and is bonded via a    ring carbon atom, wherein the phenyl and the heterocycle all are    optionally substituted by one or more identical or different    substituents chosen from the series consisting of halogen,    (C₁-C₆)-alkyl, (C₃-C₇)-cycloalkyl, HO—, (C₁-C₆)-alkyl-O—,    (C₁-C₆)-alkyl-S(O)_(m)—, H₂N—S(O)₂—, (C₁-C₄)-alkyl-NH—S(O)₂—,    di((C₁-C₄)-alkyl)N—S(O)₂— and NC—;-   R⁴⁰ is chosen from the series consisting of hydrogen and    (C₁-C₄)-alkyl;-   or R³⁰ and R⁴⁰ together are (CH₂)_(x) which is optionally    substituted by one or more identical or different (C₁-C₄)-alkyl    substituents, wherein x is an integer chosen from the series    consisting of 2, 3, 4 and 5;-   R⁵⁰ is chosen from the series consisting of hydrogen, (C₁-C₆)-alkyl,    HO— and (C₁-C₆)-alkyl-O—;-   R⁶⁰ is chosen from the series consisting of hydrogen and    (C₁-C₆)-alkyl;-   or R⁵⁰ and R⁶⁰ together are (CH₂)_(y) which is optionally    substituted by one or more identical or different (C₁-C₄)-alkyl    substituents, wherein y is an integer chosen from the series    consisting of 2, 3, 4 and 5;-   R⁷¹ is chosen from the series consisting of hydrogen and    (C₁-C₈)-alkyl which is optionally substituted by one or more    identical or different substituents chosen from the series    consisting (C₁-C₆)-alkyl-O— and (C₁-C₆)-alkyl-C(O)—O—;-   R⁷² is chosen from the series consisting of hydrogen, (C₁-C₆)-alkyl,    (C₃-C₆)-cycloalkyl, —CH₂—(CH₂)_(b)—(C₃-C₆)-cycloalkyl, Het⁴ and    —(CH₂)_(b)—Het⁴, where alkyl or cycloalkyl is optionally substituted    by one or more identical or different substituents chosen from the    series consisting of halogen, HO—, HOOC—, (C₁-C₆)-alkyl-O— and    (C₁-C₆)-alkyl-C(O)—O—, NC—, N((C₁-C₄)-alkyl)₂ and b is 0, 1 or 2;-   R⁷³ is chosen from the series consisting of hydrogen, (C₁-C₆)-alkyl;-   or-   R⁷² and R⁷³ together with the nitrogen atom to which they are bonded    form a saturated 4-membered to 7-membered monocyclic heterocycle,    which contain optionally one further ring heteroatom chosen from the    series consisting of nitrogen, oxygen and sulfur, which is    optionally substituted by one or more identical or different    substituents chosen from the series consisting of halogen,    (C₁-C₄)-alkyl, HO— and (C₁-C₄)-alkyl-O—;-   Ar, independently of each other group Ar, is chosen from the series    consisting of phenyl and an aromatic 5-membered or 6-membered    monocyclic heterocycle which comprises one, two or three identical    or different ring heteroatoms chosen from the series consisting of    nitrogen, oxygen and sulfur and is bonded via a ring carbon atom,    wherein the phenyl and the heterocycle all are optionally    substituted by one or more identical or different substituents    chosen from the series consisting of halogen, (C₁-C₆)-alkyl,    (C₁-C₆)-alkyl-O—, —O—CH₂—O—, —O—CF₂—O—, (C₁-C₆)-alkyl-S(O)_(m)—,    H₂N—S(O)₂— and NC—;-   Het¹, independently of each other group Het¹, is a saturated or    unsaturated 4-membered to 8-membered monocyclic heterocycle which    comprises a ring nitrogen atom via which Het¹ is bonded and    optionally one or two identical or different further ring    heteroatoms chosen from the series consisting of nitrogen, oxygen    and sulfur, which is optionally substituted by one or more identical    or different substituents chosen from the series consisting of    halogen, (C₁-C₄)-alkyl, HO—, (C₁-C₄)-alkyl-O—, oxo and NC—;-   Het² is a saturated 4-membered to 7-membered monocyclic heterocycle    which comprises a ring nitrogen atom via which Het² is bonded and    optionally one further ring heteroatom chosen from the series    consisting of nitrogen, oxygen and sulfur, which is optionally    substituted by one or more identical or different substituents    chosen from the series consisting of halogen, (C₁-C₄)-alkyl, HO— and    (C₁-C₄)-alkyl-O—;-   Het³, independently of each other group Het³, is a saturated    4-membered to 7-membered monocyclic heterocycle which comprises one    or two identical or different ring heteroatoms chosen from the    series consisting of nitrogen, oxygen and sulfur and is bonded via a    ring carbon atom, which is optionally substituted by one or more    identical or different substituents chosen from the series    consisting of fluorine, (C₁-C₄)-alkyl and oxo;-   Het⁴, independently of each other group Het⁴, is a saturated or    unsaturated 4-membered to 8-membered monocyclic heterocycle which    comprises one to four ring heteroatoms chosen from the series    consisting of nitrogen, oxygen and sulfur which is optionally    substituted by one or more identical or different substituents    chosen from the series consisting of halogen, (C₁-C₄)-alkyl, HO—,    (C₁-C₄)-alkyl-O—, oxo and NC—;-   m, independently of each other number m, is an integer chosen from    the series consisting of 0, 1 and 2;-   wherein all cycloalkyl groups, independently of each other, are    optionally substituted by one or more identical or different    substituents chosen from the series consisting of fluorine and    (C₁-C₄)-alkyl;-   wherein all alkyl, C_(s)H_(2s), C_(u)H_(2u), (CH₂)_(x) and (CH₂)_(y)    groups, independently of each other, and independently of any other    substituents, are optionally substituted by one or more fluorine    substituents.

If structural elements such as groups, substituents or numbers, forexample, can occur several times in the compounds of the formula I, theyare all independent of each other and can in each case have any of theindicated meanings, and they can in each case be identical to ordifferent from any other such element. In a dialkylamino group, forexample, the alkyl groups can be identical or different.

Alkyl groups, i.e. saturated hydrocarbon residues, can be linear(straight-chain) or branched. This also applies if these groups aresubstituted or are part of another group, for example an alkyl-O— group(alkyloxy group, alkoxy group) or an HO-substituted alkyl group(hydroxyalkyl group). Depending on the respective definition, the numberof carbon atoms in an alkyl group can be 1, 2, 3, 4, 5, 6, 7, 8, 9 or10, or 1, 2, 3, 4, 5, 6, 7 or 8, or 1, 2, 3, 4, 5 or 6, or 1, 2, 3 or 4,or 1, 2 or 3, or 1 or 2, or 1, for example. In one embodiment of theinvention, a (C₁-C₁₀)-alkyl group present in the compounds of theformula I is a (C₁-C₈)-alkyl group, in another embodiment a(C₁-C₆)-alkyl group, in another embodiment a (C₁-C₄)-alkyl group, inanother embodiment a (C₁-C₃)-alkyl group, in another embodiment a(C₁-C₂)-alkyl group, in another embodiment a (C₂-C₃)-alkyl group, inanother embodiment a methyl group. In one embodiment of the invention, a(C₁-C₈)-alkyl group present in any position of the compounds of theformula I is a (C₁-C₆)-alkyl group, in another embodiment a(C₁-C₄)-alkyl group, in another embodiment a (C₁-C₃)-alkyl group, inanother embodiment a (C₁-C₂)-alkyl group, in another embodiment a(C₂-C₃)-alkyl group, in another embodiment a methyl group, where any(C₁-C₈)-alkyl group present in the compounds of the formula I canindependently of each other (C₁-C₈)-alkyl group be a group of any ofthese embodiments. In one embodiment of the invention, a (C₁-C₆)-alkylgroup present in any position of the compounds of the formula I is a(C₁-C₄)-alkyl group, in another embodiment a (C₁-C₃)-alkyl group, inanother embodiment a (C₁-C₂)-alkyl group, in another embodiment a(C₂-C₃)-alkyl group, in another embodiment a methyl group, where any(C₁-C₆)-alkyl group present in the compounds of the formula I canindependently of each other (C₁-C₆)-alkyl group be a group of any ofthese embodiments. In one embodiment of the invention, a (C₁-C₄)-alkylgroup present in any position of the compounds of the formula I is a(C₁-C₃)-alkyl group, in another embodiment a (C₁-C₂)-alkyl group, inanother embodiment a (C₂-C₃)-alkyl group, in another embodiment a methylgroup, where any (C₁-C₄)-alkyl group present in the compounds of theformula I can independently of each other (C₁-C₄)-alkyl group be a groupof any of these embodiments. Examples of alkyl groups are methyl, ethyl,propyl groups including propyl (i.e. n-propyl) and isopropyl, butylgroups including butyl (i.e. n-butyl), sec-butyl, isobutyl andtert-butyl, pentyl groups including pentyl (i.e. n-pentyl),1-methylbutyl, isopentyl, neopentyl and tert-pentyl, hexyl groupsincluding hexyl (i.e. n-hexyl), 3,3-dimethylbutyl and isohexyl, heptylgroups including heptyl (i.e. n-heptyl), octyl groups including octyl(i.e. n-octyl), nonyl groups including nonyl (i.e. n-nonyl), and decylgroups including decyl (i.e. n-decyl). Examples of alkyl-O— groups aremethoxy, ethoxy, propoxy (i.e. n-propoxy), isopropoxy, butoxy (i.e.n-butoxy), isobutoxy, tert-butoxy, pentoxy (i.e. n-pentoxy). Examples ofalkyl-S(O)_(m)— are methylsulfanyl-(CH₃—S—),methanesulfinyl-(CH₃—S(O)—), methanesulfonyl (CH₃—S(O)₂—),ethylsulfanyl-(CH₃—CH₂—S—), ethanesulfinyl-(CH₃—CH₂—S(O)—),ethanesulfonyl (CH₃—CH₂—S(O)₂—), 1-methylethylsulfanyl-((CH₃)₂CH—S—),1-methylethanesulfinyl-((CH₃)₂CH—S(O)—), 1-methylethanesulfonyl((CH₃)₂CH—S(O)₂—). In one embodiment of the invention the number m ischosen from 0 and 2, wherein all numbers m are independent of each otherand can be identical or different. In another embodiment the number m inany of its occurrences is, independently of its meaning in otheroccurrences, 0. In another embodiment the number m in any of itsoccurrences is, independently of its meaning in other occurrences, 2.

A substituted alkyl group can be substituted in any positions, providedthat the respective compound is sufficiently stable and is suitable as apharmaceutical active compound. The prerequisite that a specific groupand a compound of the formula I are sufficiently stable and suitable asa pharmaceutical active compound, applies in general with respect to thedefinitions of all groups in the compounds of the formula I. In oneembodiment of the invention, an individual carbon atom in any alkylgroup in the compounds of the formula I, as well as in other groups suchas cycloalkyl groups and heterocyclic groups, for example, independentlyof any other carbon atom does not carry more than one substituent whichis bonded via an oxygen atom, nitrogen atom or sulfur atom, such as HO—,(C₁-C₄)-alkyl-O— or (C₁-C₄)-alkyl-S(O)_(m)-substituents, for example. Analkyl group which is optionally substituted by one or more fluorinesubstituents can be unsubstituted, i.e. not carry fluorine substituents,or substituted, for example by one, two, three, four, five, six, seven,eight, nine, ten or eleven fluorine substituents, or by one, two, three,four, five, six or seven fluorine substituents, or by one, two, three,four or five fluorine substituents, or by one, two or three fluorinesubstituents, which can be located in any positions. For example, in afluoro-substituted alkyl group one or more methyl groups can carry threefluorine substituents each and be present as trifluoromethyl groups,and/or one or more methylene groups (CH₂) can carry two fluorinesubstituents each and be present as difluoromethylene groups. Theexplanations with respect to the substitution of a group by fluorinealso apply if the group additionally carries other substituents and/oris part of another group, for example of an alkyl-O— group. Examples offluoro-substituted alkyl groups are trifluoromethyl, 2-fluoroethyl,1-fluoroethyl, 1,1-difluoroethyl, 2,2,2-trifluoroethyl,pentafluoroethyl, 3,3,3-trifluoropropyl, 2,2,3,3,3-pentafluoropropyl,4,4,4-trifluorobutyl and heptafluoroisopropyl. Examples offluoro-substituted alkyl-O— groups are trifluoromethoxy,2,2,2-trifluoroethoxy, pentafluoroethoxy and 3,3,3-trifluoropropoxy.Examples of fluoro-substituted alkyl-S(O)_(m)— groups aretrifluoromethylsulfanyl-(CF₃—S—), trifluoromethanesulfinyl-(CF₃—S(O)—)and trifluoromethanesulfonyl (CF₃—S(O)₂—).

The above explanations with respect to alkyl groups applycorrespondingly to alkanediyl groups (divalent alkyl groups) includingthe divalent groups C_(s)H_(2s), C_(u)H_(2u), (CH₂)_(x) and (CH₂)_(y).Also the alkyl part of a substituted alkyl group may be regarded as analkanediyl group. Thus, alkanediyl groups can also be linear orbranched, the bonds to the adjacent groups can be located in anypositions and can start from the same carbon atom or from differentcarbon atoms, and they can be substituted by fluorine substituents.Examples of alkanediyl groups including the groups C_(s)H_(2s) andC_(u)H_(2u) and, as far they constitute polymethylene chains, the groups(CH₂)_(x) are —CH₂—, —CH₂—CH₂—, —CH₂—CH₂—CH₂—, —CH₂—CH₂—CH₂—CH₂—,—CH₂—CH₂—CH₂—CH₂—CH₂—, —CH(CH₃)—, —C(CH₃)₂—, —CH(CH₃)—CH₂—,—CH₂—CH(CH₃)—, —C(CH₃)₂—CH₂—, —CH₂—C(CH₃)₂—. Examples offluoro-substituted alkanediyl groups, which can contain one, two, three,four, five or six fluorine substituents, or one, two, three or fourfluorine substituents, or one or two fluorine substituents, for example,are —CHF—, —CF₂— —CF₂—CH₂—, —CH₂—CF₂—, —CF₂—CF₂—, —CF(CH₃)—, —C(CF₃)₂—,—C(CH₃)₂—CF₂—, —CF₂—C(CH₃)₂—.

The number of ring carbon atoms in a (C₃-C₇)-cycloalkyl group can be 3,4, 5, 6 or 7. Examples of cycloalkyl are cyclopropyl, cyclobutyl,cyclopentyl, cyclohexyl and cycloheptyl. As regards the optionalsubstitution of cycloalkyl groups by one or more (C₁-C₄)-alkylsubstituents, they be unsubstituted, i.e. not carry alkyl substituents,or substituted, for example by one, two, three or four, or by one ortwo, identical or different (C₁-C₄)-alkyl substituents, for example bymethyl groups, which substituents can be located in any positions.Examples of such alkyl-substituted cycloalkyl groups are1-methylcyclopropyl, 2,2-dimethylcyclopropyl, 1-methylcyclopentyl,2,3-dimethylcyclopentyl, 1-methylcyclohexyl, 4-methylcyclohexyl,4-isopropylcyclohexyl, 4-tert-butylcyclohexyl and3,3,5,5-tetramethylcyclohexyl. As regards the optional substitution ofcycloalkyl groups by one or more fluorine substituents, they can beunsubstituted, i.e. not carry fluorine substituents, or substituted, forexample by one, two, three, four, five, six, seven, eight, nine, ten oreleven fluorine substituents, or by one, two, three, four, five or sixfluorine substituents, or by one, two, three or four fluorinesubstituents, or by one or two fluorine substituents. The fluorinesubstituents can be located in any positions of the cycloalkyl group andcan also be located in an alkyl substituent on the cycloalkyl group.Examples of fluoro-substituted cycloalkyl groups are1-fluorocyclopropyl, 2,2-difluorocyclopropyl, 3,3-difluorocyclobutyl,1-fluorocyclohexyl, 4,4-difluorocyclohexyl and3,3,4,4,5,5-hexafluorocyclohexyl. Cycloalkyl groups can also besubstituted simultaneously by fluorine and alkyl. Examples of(C₃-C₇)-cycloalkyl-substituted alkyl groups, which can represent R¹¹ orR³⁰, for example, are cyclopropylmethyl-, cyclobutylmethyl-,cyclopentylmethyl-, cyclohexylmethyl-, cycloheptylmethyl-,1-cyclopropylethyl-, 2-cyclopropylethyl-, 1-cyclobutylethyl-,2-cyclobutylethyl-, 1-cyclopentylethyl-, 2-cyclopentylethyl-,1-cyclohexylethyl-, 2-cyclohexylethyl-, 1-cycloheptylethyl-,2-cycloheptylethyl-. The explanations with respect cycloalkyl groupsapply correspondingly to divalent cycloalkyl groups (cycloalkanediylgroups), which can occur in case the two groups R³⁰ and R⁴⁰ together are(CH₂)_(x) or the two groups R⁵⁰ and R⁶⁰ together are (CH₂)_(y). Also thecycloalkyl part of a substituted cycloalkyl group may be regarded as acycloalkanediyl group. Thus, for example, the bonds through which acycloalkanediyl group is connected to the adjacent groups, can belocated in any positions and can start from the same ring carbon atom,as in the case of the cycloalkanediyl group which is present if R³⁰ andR⁴⁰ together are (CH₂)_(x) or the two groups R⁵⁰ and R⁶⁰ together are(CH₂)_(y), or from different ring carbon atoms.

In substituted phenyl groups the substituents can be located in anypositions. In the case a the divalent substituents —O—CH₂—O—(methylenedioxy) and —O—CF₂-β-(difluoromethylenedioxy) which can bepresent on phenyl groups and aromatic heterocycles, the two oxygen atomsare bonded to adjacent ring carbon atoms of the phenyl group or thearomatic heterocycle and replace two hydrogen atoms of the parentsystem. In monosubstituted phenyl groups, the substituent can be locatedin the 2-position, the 3-position or the 4-position. In disubstitutedphenyl groups, the substituents can be located in 2,3-position,2,4-position, 2,5-position, 2,6-position, 3,4-position or 3,5-position.In trisubstituted phenyl groups, the substituents can be located in2,3,4-position, 2,3,5-position, 2,3,6-position, 2,4,5-position,2,4,6-position or 3,4,5-position. If a phenyl group carries foursubstituents, some of which can be fluorine atoms, for example, thesubstituents can be located in 2,3,4,5-position, 2,3,4,6-position or2,3,5,6-position. If a polysubstituted phenyl group carries differentsubstituents, each substituent can be located in any suitable position,and the present invention comprises all positional isomers. The numberof substituents in an optionally substituted phenyl group can be one,two, three, four or five. In one embodiment of the invention, anoptionally substituted phenyl group, independently of any otheroptionally substituted phenyl group in a compound of the formula I,carries one, two, three or four, in another embodiment one, two orthree, in another embodiment one or two, in another embodiment one,identical or different substituents, and in another embodiment it isunsubstituted.

Likewise, in substituted heterocyclic groups, including aromatic5-membered and 6-membered monocyclic heterocycles which can representR³², R³³ and Ar, saturated and unsaturated 4-membered to 8-memberedmonocyclic heterocycles which can represent Het¹, and saturated4-membered to 7-membered monocyclic heterocycles which can representHet² and Het³, the substituents can be located in any positions and canbe present on ring carbon atoms and/or on suitable ring nitrogen atoms.The present invention comprises all positional isomers. The number ofsubstituents which can be present on substituted heterocycles in thecompounds of the formula I, depends on the ring size, the number andtype of the ring heteroatoms and the degree of unsaturation. In oneembodiment of the invention, the number of identical or differentsubstituents on any of the heterocyclic groups in the compounds of theformula I, independently of the number of substituents in any otheroccurrence of this group and the number of substituents in any otherheterocyclic group in the compounds of the formula I, is one, two,three, four or five, in another embodiment one, two, three or four, inanother embodiment one, two or three, in another embodiment one or two,in another embodiment one. Ring nitrogen atoms which optionally carry asubstituent, include ring nitrogen atoms in saturated heterocyclic ringsother than those via which such a ring is bonded, and the ring nitrogenatom in 5-membered aromatic heterocycles such as pyrrole, imidazole ortriazole, which in the parent heterocycle carry a hydrogen atom. In oneembodiment of the invention, the substituents on any such ring nitrogenatoms in heterocyclic groups are chosen from those of the substituentsspecified in the definition of the respective group which are bonded viaa carbon atom, for example from the series consisting of (C₁-C₆)-alkyl,(C₃-C₇)-cycloalkyl and R³³, in another embodiment from the seriesconsisting of (C₁-C₆)-alkyl and (C₃-C₇)-cycloalkyl, in the case of thearomatic heterocycle which can represent R³², from the series consistingof (C₁-C₆)-alkyl and (C₃-C₇)-cycloalkyl in the case of the aromaticheterocycle which can represent R³³, and are (C₁-C₆)-alkyl in the caseof the aromatic heterocycle which can represent Ar and (C₁-C₄)-alkyl inthe case of Het¹, Het² and Het³. Generally, besides optionally carryingthe substituents indicated in the definition of the respective group,suitable ring nitrogen atoms in heterocyclic groups in the compounds ofthe formula I, in particular aromatic heterocyclic groups such as theheterocyclic groups which can represent R³², R³³ and Ar, for example thering nitrogen atom in a pyridinyl group, can also carry an oxidosubstituent —O⁻ and be present as an N-oxide.

The ring heteroatoms specified in the definitions of heterocyclic groupsin the compounds of the formula I, including the aromatic 5-membered and6-membered monocyclic heterocycles which can represent R³², R³³ and Arand the heterocycles which represent Het¹, Het², Het³ and Het⁴ cangenerally be present in any combination and located in any suitable ringpositions, provided that the resulting group and the compound of theformula I are sufficiently stable and suitable as a pharmaceuticalactive compound, as mentioned above. In one embodiment of the invention,two oxygen atoms in any heterocyclic ring in the compounds of theformula I cannot be present in adjacent ring positions. In anotherembodiment, two ring heteroatoms in any non-aromatic heterocyclic ringin the compounds of the formula I cannot be present in adjacent ringpositions. In another embodiment, two ring heteroatoms chosen from theseries consisting of N atoms which carry a hydrogen atom or asubstituent and are bonded to the adjacent ring atoms by single bonds, Oatoms and S atoms in a non-aromatic heterocycle cannot be present inadjacent ring positions. In an aromatic heterocycle the choice of ringheteroatoms and their positions is limited by the prerequisite that thering is aromatic, i.e., it comprises a cyclic system of six delocalizedpi electrons. Thus, for example, in an aromatic monocyclic 6-memberedheterocycle only nitrogen atoms can occur as ring heteroatoms, and in anaromatic monocyclic 5-membered heterocycle only one ring heteroatomchosen from the series consisting of O atoms, S atoms and N atomscarrying a hydrogen atom or a substituent, can be present. Anunsaturated heterocycle which can represent Het¹, can be aromatic, forexample in the case of a pyrrolyl, imidazolyl or triazolyl group whichis bonded via a ring nitrogen atom and can represent Het¹, ornon-aromatic and comprise one or two double bonds within the ring whichcan be present in any positions. In one embodiment, a 4-memberedheterocycle representing Het¹ cannot be unsaturated. A heterocyclicgroup can be bonded via any ring carbon atom or via any suitable ringnitrogen atom, respectively, as indicated in the definition of therespective group. The group Het¹ can be 4-membered, 5-membered,6-membered or 7-membered or 8-membered. The groups Het² and Het³ can be4-membered, 5-membered, 6-membered or 7-membered.

Examples of aromatic heterocycles, from any one or more of which thearomatic 5-membered and 6-membered monocyclic heterocycles which canrepresent R³², R³³ and Ar and, as far as applicable, the group Het¹ arechosen in one embodiment of the invention, are pyrrole, furan,thiophene, imidazole, pyrazole, oxazole ([1,3]oxazole), isoxazole([1,2]oxazole), thiazole ([1,3]thiazole), isothiazole ([1,2]thiazole),[1,2,3]triazole, [1,2,4]triazole, [1,3,4]oxadiazole, pyridine,pyridazine, pyrimidine and pyrazine, which can all be bonded via anyring carbon atom or via any suitable ring nitrogen atom, and which allare optionally substituted as indicated with respect to the compounds offormula I in general or in any embodiment specified above or below.Examples of specific residues of aromatic heterocycles, from any one ormore of which the aromatic, 5-membered or 6-membered monocyclicheterocyclic residue which can represent R³², R³³ or Ar and, as far asapplicable, the group Het¹, are chosen in one embodiment of theinvention, are pyrrol-1-yl, pyrrol-2-yl, pyrrol-3-yl, furan-2-yl,furan-3-yl, thiophen-2-yl (2-thienyl), thiophen-3-yl (3-thienyl),imidazol-1-yl, imidazol-2-yl, imidazol-4-yl, imidazol-5-yl,pyrazol-1-yl, pyrazol-3-yl, pyrazol-4-yl, pyrazol-5-yl, oxazol-2-yl,oxazol-4-yl, oxazol-5-yl, isoxazol-3-yl, isoxazol-4-yl, isoxazol-5-yl,thiazol-2-yl, thiazol-4-yl, thiazol-5-yl, isothiazol-3-yl,isothiazol-4-yl, isothiazol-5-yl, [1,2,3]triazol-1-yl,[1,2,3]triazol-4-yl, [1,2,3]triazol-5-yl, [1,2,4]triazol-1-yl,[1,2,4]triazol-3-yl, [1,2,4]triazol-4-yl, [1,3,4]oxadiazol-2-yl,pyridin-2-yl (2-pyridyl), pyridin-3-yl (3-pyridyl), pyridin-4-yl(4-pyridyl), pyridazin-3-yl, pyridazin-4-yl, pyrimidin-2-yl,pyrimidin-4-yl, and pyrazin-2-yl, which all are optionally substitutedas indicated with respect to the compounds of formula I in general or inany embodiment specified above or below.

Examples of saturated heterocycles and non-aromatic unsaturatedheterocycles, from any one or more of which the groups Het¹, Het², Het³and Het⁴ are independently of each other chosen in one embodiment of theinvention, as far as applicable with regard to the ring size and thedegree of saturation, are azetidine, oxetane, thietane, pyrrolidine,2,5-dihydro-1H-pyrrole, tetrahydrofuran, tetrahydrothiophene,pyrazolidine, imidazolidine, 4,5-dihydro-1H-imidazole, [1,3]dioxolane,oxazolidine, thiazolidine, piperidine, 1,2,3,6-tetrahydropyridine,tetrahydropyran, tetrahydrothiopyran, piperazine, [1,3]dioxane,[1,4]dioxane, morpholine, thiomorpholine, azepane, oxepane, thiepane,[1,3]diazepane, [1,4]diazepane, [1,4]oxazepane, [1,4]thiazepane andazocane, which all are optionally substituted as indicated with respectto the compounds of formula I in general or in any embodiment specifiedabove or below. Examples of specific residues of saturated andnon-aromatic unsaturated heterocycles, from any one or more of which thegroups Het¹, Het², Het³ and Het⁴ are independently of each other chosenin one embodiment of the invention, as far as applicable with regard tothe ring size, the degree of saturation and the kind of the atom viawhich the residue is bonded are azetidin-1-yl, oxetan-3-yl,thietan-3-yl, pyrrolidin-1-yl, pyrrolidin-2-yl, pyrrolidin-3-yl,2,5-dihydro-1H-pyrrol-1-yl, tetrahydrofuran-2-yl, tetrahydrofuran-3-yl,tetrahydrothiophen-2-yl, tetrahydrothiophen-3-yl, pyrazolidin-1-yl,pyrazolidin-4-yl, imidazolidin-1-yl, imidazolidin-2-yl,imidazolidin-4-yl, 4,5-dihydro-1H-imidazol-2-yl, 1,3-dioxolan-2-yl,1,3-dioxolan-4-yl, oxazolidin-2-yl, oxazolidin-3-yl, oxazolidin-4-yl,oxazolidin-5-yl, thiazolidin-2-yl, thiazolidin-3-yl, thiazolidin-4-yl,thiazolidin-5-yl, piperidin-1-yl, piperidin-2-yl, piperidin-3-yl,piperidin-4-yl, 1,2,3,6-tetrahydropyridin-1-yl, tetrahydropyran-2-yl,tetrahydropyran-3-yl, tetrahydropyran-4-yl, tetrahydrothiopyran-2-yl,tetrahydrothiopyran-3-yl, tetrahydrothiopyran-4-yl, piperazin-1-yl,piperazin-2-yl, [1,3]dioxan-2-yl, [1,3]dioxan-4-yl, [1,3]dioxan-5-yl,[1,4]dioxan-2-yl, morpholin-2-yl, morpholin-3-yl, morpholin-4-yl,thiomorpholin-2-yl, thiomorpholin-3-yl, thiomorpholin-4-yl, azepan-1-yl,azepan-2-yl, azepan-3-yl, azepan-4-yl, oxepan-2-yl, oxepan-3-yl,oxepan-4-yl, [1,3]diazepan-1-yl, [1,4]diazepan-1-yl, [1,4]oxazepan-1-yland [1,4]thiazepan-1-yl, which all are optionally substituted asindicated with respect to the compounds of formula I in general or inany embodiment specified above or below.

Halogen is fluorine, chlorine, bromine or iodine. In one embodiment ofthe invention, halogen in any occurrence in the compounds of the formulaI, independently of all other occurrences, is fluorine, chlorine orbromine, in another embodiment fluorine or chlorine, in anotherembodiment fluorine.

An oxo substituent, i.e. an oxygen atom which is bonded via a doublebond, when bonded to a carbon atom, replaces two hydrogen atoms on thecarbon atom of the parent system to which it is bonded. Thus, if a CH₂group is substituted by oxo, it becomes a carbonyl group (C(O), C═O). Anoxo substituent cannot be present on a carbon atom in an aromatic ring.Besides on carbon atoms, oxo substituents can also be present on a ringsulfur atom in the group Het¹, in particular if the group Het¹ issaturated, and in the group Het³, to give the ring member S(O) (S═O,i.e. a sulfoxide group), if one oxo substituent is present on the sulfuratom, or the ring member S(O)₂ (S(═O)₂, i.e. a sulfone group), if twooxo substituents are present on the sulfur atom. As examples ofheterocycles which can represent Het¹ and Het³ and which carry oxosubstituent a ring sulfur atom, 1,1-dioxo-tetrahydrothiophene,1-oxo-thiomorpholine and 1,1-dioxo-thiomorpholine may be mentioned,which all are optionally substituted by further substituents such as(C₁-C₄)-alkyl substituents as indicated with respect to the compounds offormula I in general or in any embodiment specified above or below.

The present invention comprises all stereoisomeric forms of thecompounds of the formula I, for example all enantiomers anddiastereomers including cis/trans isomers. The invention likewisecomprises mixtures of two or more stereoisomeric forms, for examplemixtures of enantiomers and/or diastereomers including cis/transisomers, in all ratios. Asymmetric centers contained in the compounds ofthe formula I, for example in unsubstituted or substituted alkyl groups,can all independently of each other have the S configuration or the Rconfiguration. The invention relates to enantiomers, both thelevorotatory and the dextrorotatory antipode, in enantiomerically pureform and essentially enantiomerically pure form, for example with amolar ratio of the two enantiomers of 99:1 or greater, and in the formof racemates and in the form of mixtures of the two enantiomers in allratios. The invention likewise relates to diastereomers in the form ofpure and essentially pure diastereomers and in the form of mixtures oftwo or more diastereomers in all ratios. The invention also comprisesall cis/trans isomers of the compounds of the formula I in pure form andessentially pure form, for example with a molar ratio of the cis/transisomers of 99:1 or greater, and in the form of mixtures of the cisisomer and the trans isomer in all ratios. Cis/trans isomerism can occurin substituted rings. The preparation of individual stereoisomers, ifdesired, can be carried out by resolution of a mixture according tocustomary methods, for example, by chromatography or crystallization, orby use of stereochemically uniform starting compounds in the synthesisor by stereoselective reactions. Optionally, before a separation ofstereoisomers a derivatization can be carried out. The separation of amixture of stereoisomers can be carried out at the stage of the compoundof the formula I or at the stage of an intermediate in the course of thesynthesis. The invention also comprises all tautomeric forms of thecompounds of the formula I.

Physiologically acceptable salts, including pharmaceutically utilizablesalts, of the compounds of the formula I generally comprise a nontoxicsalt component. They can contain inorganic or organic salt components.Such salts can be formed, for example, from compounds of the formula Iwhich contain an acidic group, for example a carboxylic acid group(hydroxycarbonyl group, HO—C(O)—), and nontoxic inorganic or organicbases. Suitable bases are, for example, alkali metal compounds oralkaline earth metal compounds, such as sodium hydroxide, potassiumhydroxide, sodium carbonate or sodium hydrogencarbonate, or ammonia,organic amino compounds and quaternary ammonium hydroxides. Reactions ofcompounds of the formula I with bases for the preparation of the saltsare in general carried out according to customary procedures in asolvent or diluent. Examples of salts of acidic groups thus are sodium,potassium, magnesium or calcium salts or ammonium salts which can alsocarry one or more organic groups on the nitrogen atom. Compounds of theformula I which contain a basic, i.e. protonatable, group, for examplean amino group or a basic heterocycle, can be present in the form oftheir acid addition salts with physiologically acceptable acids, forexample as salt with hydrogen chloride, hydrogen bromide, phosphoricacid, sulfuric acid, acetic acid, benzoic acid, methanesulfonic acid,p-toluenesulfonic acid, which in general can be prepared from thecompounds of the formula I by reaction with an acid in a solvent ordiluent according to customary procedures. If the compounds of theformula I simultaneously contain an acidic and a basic group in themolecule, the invention also includes internal salts (betaines,zwitterions) in addition to the salt forms mentioned. The presentinvention also comprises all salts of the compounds of the formula Iwhich, because of low physiological tolerability, are not directlysuitable for use as a pharmaceutical, but are suitable as intermediatesfor chemical reactions or for the preparation of physiologicallyacceptable salts, for example by means of anion exchange or cationexchange. The present invention also comprises all solvates of thecompounds of the formula I and their salts, including physiologicallyacceptable solvates, such as hydrates, i.e. adducts with water, andadducts with alcohols like (C₁-C₄)-alkanols, as well as activemetabolites of compounds of the formula I and prodrugs of the compoundsof the formula I, i.e. compounds which in vitro may not necessarilyexhibit pharmacological activity but which in vivo are converted intopharmacologically active compounds of the formula I, for examplecompounds which are converted by metabolic hydrolysis into a compound ofthe formula I, such as compounds in which a carboxylic acid group ispresent in esterified form or in the form of an amide.

In one embodiment of the invention, the group A is C(R¹), in anotherembodiment A is N. In one embodiment of the invention, the group D ischosen from the series consisting of N(R²) and O, in another embodimentfrom the series consisting of N(R²) and S, in another embodiment fromthe series consisting of O and S, in another embodiment D is N(R²), inanother embodiment D is O, in another embodiment D is S. In oneembodiment of the invention, the group E is C(R³), in another embodimentE is N. In one embodiment of the invention, one or more of the groups A,D and E have any one or some of their meanings and any remaining groupsA, D and E have all their meanings. For example, in one embodiment A ischosen from the series consisting of C(R¹) and N, D is N(R²) and E ischosen from the series consisting of C(R³) and N, in another embodimentA is chosen from the series consisting of C(R¹) and N, D is N(R²) and Eis N, in another embodiment A is C(R¹), D is N(R²) and E is chosen fromthe series consisting of C(R³) and N, in another embodiment A is C(R¹),D is N(R²) and E is N, in another embodiment A is C(R¹), D is chosenfrom the series consisting of N(R²) and O and D is N, in anotherembodiment A is N, D is chosen from the series consisting of from N(R²),O and S and E is C(R³), in another embodiment A is N, D is N(R²) and Eis chosen from the series consisting of C(R³) and N. In one embodimentof the invention, one of the groups A and D is N and the other of thegroups A and D is C(R¹) or C(R³), respectively, in another embodimentone or both of the groups A and D are N and any remaining group A or Dis C(R¹) or C(R³), respectively, in another embodiment both of thegroups A and D are N, and in another embodiment none of the groups A andD is N.

In terms of formulae resulting from formula I by incorporation ofmeanings of A, D or E, in one embodiment of the invention a compound ofthe formula I is a compound of any one or more of formulae I-1 to I-35,for example a compound of formula I-1, or a compound of formula I-2, ora compound of formula I-6, or a compound of formula I-9, or a compoundof formula I-10, or a compound of formula I-14, or a compound of formulaI-17, or a compound of formula I-19, or a compound of formula I-6 orformula I-14, or a compound of formula I-11 or formula I-12, or acompound of formula I-6 or formula I-10 or formula I-14, in any of itsstereoisomeric forms or a mixture of stereoisomeric forms in any ratio,or a physiologically acceptable salt thereof, or a physiologicallyacceptable solvate of any of them, wherein in the compounds of formulaeI-1 to 1-35 the groups A, D, E, G, R¹, R², R³, R¹⁰, R³⁰, R⁴⁰, R⁵⁰ andR⁶⁰ are defined as in the compounds of formula I in general or in anyembodiment specified above or below.

In one embodiment of the invention, the group G is chosen from theseries consisting of R⁷¹—O—C(O)—, R⁷²—N(R⁷³)—C(O)— and tetrazol-5-yl, inanother embodiment from the series consisting of R⁷¹—O—C(O)— andR⁷²—N(R⁷³)—C(O)—, in another embodiment G is R⁷¹—O—C(O)—, and in anotherembodiment G is R⁷²—N(R⁷³)—C(O)—.

In one embodiment of the invention, the group R¹ is chosen from theseries consisting of hydrogen, halogen, (C₁-C₆)-alkyl, HO—,(C₁-C₆)-alkyl-O—, and NC—, in another embodiment from the seriesconsisting of hydrogen, halogen, (C₁-C₆)-alkyl, (C₁-C₆)-alkyl-O— andNC—, in another embodiment from the series consisting of hydrogen,halogen, (C₁-C₆)-alkyl and NC—, in another embodiment from the seriesconsisting of hydrogen, halogen, (C₁-C₆)-alkyl, HO— and(C₁-C₆)-alkyl-O—, in another embodiment from the series consisting ofhydrogen, halogen, (C₁-C₆)-alkyl and (C₁-C₆)-alkyl-O—, in anotherembodiment from the series consisting of hydrogen, halogen and(C₁-C₆)-alkyl, in another embodiment from the series consisting ofhydrogen and halogen, in another embodiment from the series consistingof hydrogen, fluorine and chlorine, and in another embodiment R¹ ishydrogen. In one embodiment of the invention, a (C₁-C₆)-alkyl groupoccurring in R¹ is a (C₁-C₄)-alkyl group, in another embodiment a(C₁-C₂)-alkyl group, in another embodiment it is methyl.

In one embodiment of the invention, the group R² is chosen from theseries consisting of (C₁-C₇)-alkyl and (C₃-C₇)-cycloalkyl-C_(s)H_(2s)—,in another embodiment from the series consisting of (C₃-C₇)-cycloalkyl-CC_(s)H_(2s)— and Ar—C_(s)H_(2s)—, in another embodiment R² is(C₁-C₇)-alkyl, in another embodiment R² is (C₃-C₇)-cycloalkyl-CC_(s)H_(2s)—, and in another embodiment R² is Ar—C_(s)H_(2s)—. In oneembodiment, s is an integer chosen from the series consisting of 0, 1and 2, in another embodiment from the series consisting of 0 and 1, inanother embodiment from the series consisting of 1 and 2, in anotherembodiments is 0, and in another embodiments is 1. In one embodiment ofthe invention, R² is Ar—C_(s)H_(2s)— and s is 0, i.e., R² is the groupAr and the group D thus is the group N(Ar). In one embodiment, thedivalent alkanediyl group C_(s)H_(2s) is a linear group. In oneembodiment, a (C₁-C₇)-alkyl group representing R² is a (C₃-C₇)-alkylgroup, in another embodiment a (C₃-C₆)-alkyl group. In one embodiment, a(C₃-C₇)-cycloalkyl group occurring in R² is a (C₃-C₆)-cycloalkyl group,in another embodiment a (C₅-C₆)-cycloalkyl group, in another embodimenta cyclopropyl group. In one embodiment, a group Ar occurring in R² ischosen from the series consisting of phenyl and an aromatic 5-memberedor 6-membered heterocycle which comprises one or two identical ordifferent ring heteroatoms chosen from the series consisting ofnitrogen, oxygen and sulfur, which is bonded via a ring carbon atom, inanother embodiment from the series consisting of phenyl and an aromatic6-membered heterocycle which comprises one or two nitrogen atoms as ringheteroatoms, in another embodiment from the series consisting of phenyl,thiophenyl, pyridinyl and pyrimidinyl, in another embodiment from theseries consisting of phenyl and thiophenyl, in another embodiment fromthe series consisting of phenyl, pyridinyl and pyrimidinyl, in anotherembodiment from the series consisting of phenyl and pyridinyl, and inanother embodiment a group Ar occurring in R² is phenyl, which groupsall are optionally substituted as indicated with respect to thecompounds of formula I in general or in any embodiment specified aboveor below. In one embodiment, a group Ar occurring in R² is optionallysubstituted by one, two or three identical or different substituents, inanother embodiment it is optionally substituted by one or two identicalor different substituents, in another embodiment it is optionallysubstituted by one substituent, in another embodiment it is substitutedby one, two or three identical or different substituents, in anotherembodiment it is substituted by one or two identical or differentsubstituents, and in another embodiment it is substituted by onesubstituent. In one embodiment, the substituents which are optionallypresent on a group Ar occurring in R², are chosen from the seriesconsisting of halogen, (C₁-C₆)-alkyl, (C₁-C₆)-alkyl-O—,(C₁-C₆)-alkyl-S(O)_(m)— and NC—, in another embodiment from the seriesconsisting of halogen, (C₁-C₆)-alkyl, (C₁-C₆)-alkyl-O— and(C₁-C₆)-alkyl-S(O)_(m)—, in another embodiment from the seriesconsisting of halogen, (C₁-C₆)-alkyl and (C₁-C₆)-alkyl-S(O)_(m)—, inanother embodiment from the series consisting of halogen and(C₁-C₆)-alkyl, in another embodiment from the series consisting ofhalogen, in another embodiment from the series consisting of fluorineand chlorine, in another embodiment from the series consisting offluorine, chlorine and methyl. In one embodiment of the invention, a(C₁-C₆)-alkyl group occurring in R² is a (C₁-C₄)-alkyl group, in anotherembodiment a (C₁-C₂)-alkyl group, in another embodiment it is methyl.

Examples of groups Ar which can occur in R², and from any one or more ofwhich a group Ar occurring in R² is chosen in one embodiment of theinvention, are phenyl, 2-fluoro-phenyl, 3-fluoro-phenyl,4-fluoro-phenyl, 2-chloro-phenyl, 3-chloro-phenyl, 4-chloro-phenyl,3-bromo-phenyl, 4-bromo-phenyl, 2,3-dichloro-phenyl,2,4-dichloro-phenyl, 2,5-dichloro-phenyl, 2,6-dichloro-phenyl,3,4-dichloro-phenyl, 2,3-difluoro-phenyl, 2,4-difluoro-phenyl,2,5-difluoro-phenyl, 2,6-difluoro-phenyl, 3,4-difluoro-phenyl,2-chloro-6-fluoro-phenyl, 3,4,5-trifluoro-phenyl, 2-methyl-phenyl(o-tolyl), 3-methyl-phenyl (m-tolyl), 4-methyl-phenyl (p-tolyl),2,3-dimethyl-phenyl, 2,4-dimethyl-phenyl, 2,5-dimethyl-phenyl,2,6-dimethyl-phenyl, 3,4-dimethyl-phenyl, 2-ethyl-phenyl,3-ethyl-phenyl, 4-ethyl-phenyl, 3-isopropyl-phenyl, 3-tert-butyl-phenyl,4-tert-butyl-phenyl, 3-trifluoromethyl-phenyl, 4-trifluoromethyl-phenyl,2-fluoro-5-methyl-phenyl, 3-chloro-2-methyl-phenyl,5-chloro-2-methyl-phenyl, 5-chloro-2-fluoro-3-methyl-phenyl,2-fluoro-3-trifluoromethyl-phenyl, 2-fluoro-5-trifluoromethyl-phenyl,4-fluoro-3-trifluoromethyl-phenyl, 5-fluoro-3-trifluoromethyl-phenyl,3-chloro-4-trifluoromethyl-phenyl, 5-chloro-2-trifluoromethyl-phenyl,5-chloro-3-trifluoromethyl-phenyl, 2-methoxy-phenyl, 3-methoxy-phenyl,4-methoxy-phenyl, 3-ethoxy-phenyl, 3-propoxy-phenyl,3-isopropoxy-phenyl, 4-tert-butoxy-phenyl, 3-trifluoromethoxy-phenyl,4-trifluoromethoxy-phenyl, 3-(2,2,2-trifluoroethoxy)-phenyl,5-chloro-2-methoxy-phenyl, 3-chloro-4-methoxy-phenyl,5-fluoro-3-isopropoxy-phenyl, 2-fluoro-3-trifluoromethoxy-phenyl,4-methoxy-3,5-dimethyl-phenyl, 3-methoxy-5-trifluoromethyl-phenyl,2,3-methylenedioxy-phenyl, 2,3-difluoromethylenedioxy-phenyl,3,4-methylenedioxy-phenyl, 3,4-difluoromethylenedioxy-phenyl,3-methylsulfanyl-phenyl, 3-ethylsulfanyl-phenyl,3-trifluoromethylsulfanyl-phenyl, 3-methanesulfonyl-phenyl,3-ethanesulfonyl-phenyl, 3-sulfamoyl-phenyl, 2-cyano-phenyl,3-cyano-phenyl, 4-cyano-phenyl, thiophen-2-yl, thiophen-3-yl,3-chloro-thiophen-2-yl, 4-chloro-thiophen-2-yl, 5-chloro-thiophen-2-yl,4,5-dichloro-thiophen-2-yl, 5-chloro-thiophen-3-yl,2,5-dichloro-thiophen-3-yl, 4-methyl-thiophen-2-yl,5-methyl-thiophen-3-yl, 4,5-dimethyl-thiophen-2-yl, pyridin-2-yl,pyridin-3-yl, pyridin-4-yl, 2-chloro-pyridin-3-yl,5-chloro-pyridin-2-yl, 6-chloro-pyridin-3-yl, 2-chloro-pyridin-4-yl,2,6-dichloro-pyridin-3-yl, 6-methoxy-pyridin-3-yl,2-chloro-6-methoxy-pyridin-3-yl.

In one embodiment of the invention, the group R³ is chosen from theseries consisting of hydrogen, halogen, (C₁-C₆)-alkyl, (C₁-C₆)-alkyl-O—,and NC—, in another embodiment from the series consisting of hydrogen,halogen, (C₁-C₆)-alkyl and NC—, in another embodiment from the seriesconsisting of hydrogen, halogen, (C₁-C₆)-alkyl and (C₁-C₆)-alkyl-O—, inanother embodiment from the series consisting of hydrogen, halogen and(C₁-C₆)-alkyl, in another embodiment from the series consisting ofhydrogen and halogen, in another embodiment from the series consistingof hydrogen and (C₁-C₆)-alkyl, in another embodiment from the seriesconsisting of hydrogen, fluorine and chlorine, in another embodiment R³is hydrogen, and in another embodiment R³ is (C₁-C₆)-alkyl. In oneembodiment of the invention, a (C₁-C₆)-alkyl group occurring in R³ is a(C₁-C₄)-alkyl group, in another embodiment a (C₁-C₂)-alkyl group, inanother embodiment it is methyl.

In one embodiment of the invention, the group R¹⁰ is chosen from theseries consisting of R¹¹—O— and R¹²—N(R¹³)—C(O)—O—, in anotherembodiment from the series consisting of R¹²—N(R¹³)—C(O)—O— andHet²—C(O)—O—, and in another embodiment R¹⁰ is R¹¹—O—. In oneembodiment, the group Het² which can occur in the group R¹⁰, is asaturated 4-membered to 6-membered, in another embodiment a 5-memberedor 6-membered, in another embodiment a 5-membered, monocyclicheterocycle which, besides the ring nitrogen via which Het² is bonded,optionally comprises one further ring heteroatom chosen from the seriesnitrogen, oxygen and sulfur. In one embodiment, the group Het² which canoccur in the group R¹⁰, does not comprise a further ring heteroatombesides the ring nitrogen atom via which Het² is bonded. In oneembodiment, the number of substituents which are optionally present on agroup Het² which can occur in R¹⁰, is one, two, three or four, inanother embodiment one, two or three, in another embodiment one or two,in another embodiment one, and in another embodiment such a group Het²is unsubstituted. In one embodiment, the substituents which areoptionally present on a group Het² which can occur in the group R¹⁰, arechosen from the series consisting of fluorine, (C₁-C₄)-alkyl, HO— and(C₁-C₄)-alkyl-O—, in another embodiment from the series consisting of(C₁-C₄)-alkyl, HO— and (C₁-C₄)-alkyl-O—, in another embodiment from theseries consisting of (C₁-C₄)-alkyl and HO— and (C₁-C₄)-alkyl-O—, inanother embodiment they are (C₁-C₄)-alkyl substituents, and in anotherembodiment they are HO— substituents.

In one embodiment of the invention, the group R¹¹ is chosen from theseries consisting of hydrogen, R¹⁴, (C₃-C₇)-cycloalkyl and Het³, inanother embodiment from the series consisting of hydrogen and R¹⁴, inanother embodiment from the series consisting of hydrogen, R¹⁴ and(C₃-C₇)-cycloalkyl, in another embodiment from the series consisting of(C₃-C₇)-cycloalkyl, Ar and Het³, in another embodiment from the seriesconsisting of (C₃-C₇)-cycloalkyl and Het³, in another embodiment R¹¹ ishydrogen, in another embodiment R¹¹ is R¹⁴, and in another embodimentR¹¹ is Ar. In one embodiment, a group Ar representing R¹¹ is phenylwhich is optionally substituted as indicated with respect to thecompounds of formula I in general or in any embodiment specified aboveor below. In one embodiment, a group Ar representing R¹¹ is optionallysubstituted by one, two or three identical or different substituents, inanother embodiment it is optionally substituted by one or two identicalor different substituents, in another embodiment it is optionallysubstituted by one substituent. In one embodiment, the substituentswhich are optionally present on a group Ar representing R¹¹, are chosenfrom the series consisting of halogen, (C₁-C₄)-alkyl, (C₁-C₄)-alkyl-O—and NC—, in another embodiment from the series consisting of halogen,(C₁-C₄)-alkyl and (C₁-C₄)-alkyl-O—, in another embodiment from theseries consisting of halogen and (C₁-C₄)-alkyl. In one embodiment, a(C₃-C₇)-cycloalkyl group representing R¹¹ is a (C₃-C₆)-cycloalkyl group.In one embodiment, a group Het³ representing R¹¹ is a saturated4-membered to 6-membered monocyclic heterocycle which comprises one ortwo identical or different ring heteroatoms, in another embodiment onering heteroatom, which are chosen from the series consisting ofnitrogen, oxygen and sulfur, in another embodiment it comprises one ringheteroatom chosen from the series consisting of nitrogen and oxygen, inanother embodiment one ring heteroatom chosen from the series consistingof oxygen and sulfur, and in another embodiment it comprises one oxygenatom as ring heteroatom, wherein the heterocycle is bonded via a ringcarbon atom and is optionally substituted by one, two, three or four, inanother embodiment by one or two, identical or different substituentschosen from the series consisting of fluorine, (C₁-C₄)-alkyl and oxo, inanother embodiment from the series consisting of fluorine and(C₁-C₄)-alkyl.

In one embodiment of the invention, the groups R¹² and R¹³ areindependently of each other chosen from the series consisting ofhydrogen and R¹⁵, in another embodiment from the series consisting ofR¹⁵ and Ar, and in another embodiment they are identical or differentgroups R¹⁵. In one embodiment, one of the groups R¹² and R¹³ is chosenfrom the series consisting of R¹⁵ and Ar, and the other is a group R¹⁵.In one embodiment, a group Ar representing R¹² or R¹³ is phenyl which isoptionally substituted by one or two, in another embodiment by one,identical or different substituents chosen from the series consisting ofhalogen and (C₁-C₄)-alkyl, and in another embodiment it is unsubstitutedphenyl.

In one embodiment of the invention, the (C₁-C₁₀)-alkyl grouprepresenting the group R¹⁴ is a (C₁-C₈)-alkyl group, in anotherembodiment a (C₁-C₇)-alkyl group, in another embodiment a (C₁-C₄)-alkylgroup, in another embodiment a (C₁-C₃)-alkyl group, in anotherembodiment a (C₁-C₂)-alkyl group, in another embodiment a methyl group,in another embodiment a (C₄-C₈)-alkyl group, in another embodiment a(C₄-C₇)-alkyl group, in another embodiment a (C₅-C₇)-alkyl group, inanother embodiment a C₆-alkyl group, wherein all these alkyl groups arelinear or branched as applies to alkyl groups in the compounds of theformula I in general, and are optionally substituted by one or moreidentical or different substituents as indicated with respect to thecompounds of formula I in general or in any embodiment specified aboveor below. In one embodiment of the invention, the number of optionalsubstituents in an alkyl group representing R¹⁴ is one, two, three orfour, in another embodiment one, two or three, in another embodiment oneor two, in another embodiment one. In one embodiment, an alkyl grouprepresenting R¹⁴ is unsubstituted, and in another embodiment it issubstituted by one, two, three or four, in another embodiment by one,two or three, in another embodiment by one or two, in another embodimentby one substituent as indicated.

In one embodiment, a (C₃-C₇)-cycloalkyl group occurring as a substituenton an alkyl group representing R¹⁴ is a (C₃-C₆)-cycloalkyl group, inanother embodiment it is a cyclopropyl group. In one embodiment, a groupAr occurring as a substituent on an alkyl group representing R¹⁴ isphenyl or an aromatic 5-membered or 6-membered monocyclic heterocyclewhich comprises one or two identical or different ring heteroatomschosen from the series consisting of nitrogen, oxygen and sulfur, and inanother embodiment comprises one nitrogen atom as ring heteroatom and inthe case of a 5-membered heterocycle one additional ring heteroatomchosen from the series consisting of nitrogen, oxygen and sulfur, and inanother embodiment a group Ar occurring as a substituent in an alkylgroup representing R¹⁴ is chosen from phenyl, pyrazolyl, isoxazolyl andthiazolyl, wherein all these groups Ar are optionally substituted by oneor more identical or different substituents as indicated with respect tothe compounds of formula I in general or in any embodiment specifiedabove or below. In one embodiment, the number of optional substituentson a group Ar occurring as a substituent in an alkyl group representingR¹⁴ is one, two or three, in another embodiment one or two, in anotherembodiment one. In one embodiment, the substituents which are optionallypresent on a group Ar occurring as a substituent in an alkyl grouprepresenting R¹⁴, are chosen from the series consisting of halogen,(C₁-C₄)-alkyl, (C₁-C₄)-alkyl-O— and NC—, in another embodiment from theseries consisting of halogen, (C₁-C₄)-alkyl and (C₁-C₄)-alkyl-O—, inanother embodiment from the series consisting of halogen and(C₁-C₄)-alkyl, and in another embodiment they are (C₁-C₄)-alkyl groups.

In one embodiment, a group Het¹ occurring as a substituent on an alkylgroup representing R¹⁴ is a saturated or unsaturated 4-membered to6-membered heterocycle, in another embodiment a 5-membered or 6-memberedheterocycle, which comprises a ring nitrogen atom via which Het¹ isbonded and optionally one further ring heteroatom chosen from the seriesconsisting of nitrogen, oxygen and sulfur, which is optionallysubstituted as indicated with respect to the compounds of formula I ingeneral or in any embodiment specified above or below. In oneembodiment, a group Het¹ occurring as a substituent on an alkyl grouprepresenting R¹⁴ does not comprise any further ring heteroatom besidesthe ring nitrogen atom via which Het¹ is bonded. In one embodiment, agroup Het¹ occurring as a substituent on an alkyl group representing R¹⁴is saturated, in another embodiment it is unsaturated. In oneembodiment, the number of substituents which are optionally present on agroup Het¹ occurring as a substituent on an alkyl group representing R¹⁴is one, two, three or four, in another embodiment one, two or three, inanother embodiment one or two, in another embodiment one. In oneembodiment, the substituents which are optionally present on a groupHet¹ occurring as a substituent on an alkyl group representing R¹⁴ arechosen from the series consisting of halogen, (C₁-C₄)-alkyl, HO—,(C₁-C₄)-alkyl-O— and oxo, in another embodiment from the seriesconsisting of fluorine, (C₁-C₄)-alkyl, HO— and oxo, in anotherembodiment from the series consisting of fluorine, (C₁-C₄)-alkyl andoxo, in another embodiment from the series consisting of (C₁-C₄)-alkyland oxo, and in another embodiment they are oxo substituents. In oneembodiment, the number of oxo substituents which are optionally presenton a group Het¹ occurring as a substituent on an alkyl grouprepresenting R¹⁴, is not greater than two, and in another embodiment itis not greater than one.

In one embodiment, a group Het¹ occurring in the substituent Het¹—C(O)—on an alkyl group representing R¹⁴ is a 4-membered to 6-memberedheterocycle, in another embodiment a 5-membered or 6-memberedheterocycle, which is saturated or unsaturated and comprises a ringnitrogen atom via which Het¹ is bonded and optionally one further ringheteroatom chosen from the series consisting of nitrogen, oxygen andsulfur, and which is optionally substituted as indicated with respect tothe compounds of formula I in general or in any embodiment specifiedabove or below. In one embodiment, a group Het¹ occurring in thesubstituent Het¹—C(O)— on an alkyl group representing R¹⁴ does notcomprise any further ring heteroatom besides the ring nitrogen atom viawhich Het¹ is bonded. In one embodiment, a group Het¹ occurring in thesubstituent Het¹—C(O)— on an alkyl group representing R¹⁴ is saturatedor comprises one double bond within the ring, and in another embodimentit is saturated. In one embodiment, the number of substituents which areoptionally present on a group Het¹ occurring in the substituentHet¹—C(O)— on an alkyl group representing R¹⁴ is one, two, three orfour, in another embodiment one, two or three, in another embodiment oneor two, in another embodiment one. In one embodiment, the substituentswhich are optionally present on a group Het¹ occurring in thesubstituent Het¹—C(O)— on an alkyl group representing R¹⁴ are chosenfrom the series consisting of halogen, (C₁-C₄)-alkyl, HO—,(C₁-C₄)-alkyl-O— and oxo, in another embodiment from the seriesconsisting of fluorine, (C₁-C₄)-alkyl, HO— and oxo, in anotherembodiment from the series consisting of fluorine, (C₁-C₄)-alkyl andoxo, in another embodiment from (C₁-C₄)-alkyl and oxo, in anotherembodiment they are oxo substituents, and in another embodiment they are(C₁-C₄)-alkyl substituents. In one embodiment, the number of oxosubstituents which are optionally present on a group Het¹ occurring inthe substituent Het¹—C(O)— on an alkyl group representing R¹⁴, is notgreater than two, and in another embodiment it is not greater than one,and in another embodiment no oxo substituents are present on such agroup Het¹.

In one embodiment, a group Het³ occurring as a substituent on an alkylgroup representing R¹⁴ is a saturated 4-membered to 6-memberedmonocyclic heterocycle which comprises one or two identical or differentring heteroatoms, and in another embodiment comprises one ringheteroatom, which are chosen from the series consisting of nitrogen,oxygen and sulfur, and is bonded via a ring carbon atom and isoptionally substituted as indicated with respect to the compounds offormula I in general or in any embodiment specified above or below. Inone embodiment, the ring heteroatoms in a group Het³ occurring as asubstituent on an alkyl group representing R¹⁴ are chosen from theseries consisting of nitrogen and oxygen, in another embodiment from theseries consisting of oxygen and sulfur, in another embodiment they arenitrogen atoms, and in another embodiment they are oxygen atoms. In oneembodiment, the number of substituents which are optionally present on agroup Het³ occurring as a substituent on an alkyl group representing R¹⁴is one, two, three or four, in another embodiment one, two or three, inanother embodiment one or two, in another embodiment one. In oneembodiment, the substituents which are optionally present on a groupHet³ occurring as a substituent on an alkyl group representing R¹⁴ arechosen from the series consisting of fluorine and (C₁-C₄)-alkyl, inanother embodiment from the series consisting of (C₁-C₄)-alkyl and oxo,in another embodiment they are (C₁-C₄)-alkyl substituents, and inanother embodiment they are oxo substituents. In one embodiment, thenumber of oxo substituents which are optionally present on a group Het³occurring as a substituent on an alkyl group representing R¹⁴, is notgreater than two, and in another embodiment it is not greater than one.

In one embodiment, the substituents which are optionally present on analkyl group representing R¹⁴ are chosen from the series consisting ofhalogen, HO—, R¹⁶—O—, oxo, (C₃-C₇)-cycloalkyl, Ar, Het¹, Het³,H₂N—C(O)—, (C₁-C₄)-alkyl-NH—C(O)—, di((C₁-C₄)-alkyl)N—C(O)— andHet¹—C(O)—, in another embodiment from the series consisting of halogen,HO—, R¹⁶—O—, oxo, (C₃-C₇)-cycloalkyl, Het¹, Het³, H₂N—C(O)—,(C₁-C₄)-alkyl-NH—C(O)—, di((C₁-C₄)-alkyl)N—C(O)— and Het¹—C(O)—, inanother embodiment from the series consisting of halogen, HO—, R¹⁶—O—,oxo, (C₃-C₇)-cycloalkyl, Het¹, Het³, di((C₁-C₄)-alkyl)N—C(O)— andHet¹—C(O)—, in another embodiment from the series consisting of halogen,HO—, R¹⁶—O—, oxo, (C₃-C₇)-cycloalkyl, Het¹ and Het³, in anotherembodiment from the series consisting of halogen, HO—, R¹⁶—O—, oxo,(C₃-C₇)-cycloalkyl, Ar, Het¹ and Het³, in another embodiment from theseries consisting of HO—, R¹⁶—O—, oxo, (C₃-C₇)-cycloalkyl, Ar, Het¹,di((C₁-C₄)-alkyl)N—C(O)— and Het¹—C(O)—, in another embodiment from theseries consisting of HO—, R¹⁶—O—, oxo, (C₃-C₇)-cycloalkyl, Ar,di((C₁-C₄)-alkyl)N—C(O)— and Het¹—C(O)—, in another embodiment from theseries consisting of HO—, R¹⁶—O—, oxo, (C₃-C₇)-cycloalkyl and Ar, inanother embodiment from the series consisting of HO—, R¹⁶—O—, oxo,(C₃-C₇)-cycloalkyl, di((C₁-C₄)-alkyl)N—C(O)— and Het¹—C(O)—, in anotherembodiment from the series consisting of HO—, R¹⁶—O—, oxo,(C₃-C₇)-cycloalkyl, Het¹ and Het³, in another embodiment from the seriesconsisting of HO—, R¹⁶—O—, oxo, (C₃-C₇)-cycloalkyl and Het³, in anotherembodiment from the series consisting of HO—, oxo, (C₃-C₇)-cycloalkyland Het³, in another embodiment from the series consisting of HO—, oxoand (C₃-C₇)-cycloalkyl, in another embodiment from the series consistingof HO—, oxo and Het³, in another embodiment from the series consistingof HO— and oxo, in another embodiment from the series consisting of HO—,R¹⁶—O—, (C₃-C₇)-cycloalkyl and Het³, in another embodiment from theseries consisting of HO—, (C₃-C₇)-cycloalkyl and Het³, in anotherembodiment from the series consisting of HO— and (C₃-C₇)-cycloalkyl, inanother embodiment from the series consisting of HO— and Het³, inanother embodiment they are HO— substituents, and in another embodimentthey are oxo substituents. In one embodiment, the number of oxosubstituents which are optionally present on an alkyl group representingR¹⁴, is not greater than two, and in another embodiment it is notgreater than one. In one embodiment, halogen atoms occurring assubstituents on an alkyl group representing R¹⁴, are chosen from theseries consisting of fluorine and chlorine atoms, and in anotherembodiment they are fluorine atoms and, besides being substituted by another substituents, in this latter embodiment an alkyl grouprepresenting R¹⁴ is thus optionally substituted by fluorine substituentsas applies to alkyl groups in the compounds of the formula I in general.

Examples of groups which can represent R¹⁴, and from any one or more ofwhich R¹⁴ is chosen in one embodiment of the invention, are methyl,ethyl, propyl, isopropyl, butyl, isobutyl, cyclopropylmethyl, benzyl,2-hydroxy-ethyl, 2-hydroxy-propyl, 2-hydroxy-butyl,2-hydroxy-2-methyl-propyl, 2-hydroxy-2-methyl-butyl,2-hydroxy-3-methyl-butyl, 2-hydroxy-2,3-dimethyl-butyl,2-hydroxy-3,3-dimethyl-butyl, 2-ethyl-2-hydroxy-butyl,2-hydroxy-2,3,3-trimethyl-butyl, 2-ethyl-2-hydroxy-3-methyl-butyl,2-ethyl-2-hydroxy-3,3-dimethyl-butyl, 2-cyclopropyl-2-hydroxy-ethyl,2-cyclopropyl-2-hydroxy-propyl, 2-cyclopropyl-2-hydroxy-butyl,2-oxo-propyl, 2-oxo-butyl, 3-methyl-2-oxo-butyl,3,3-dimethyl-2-oxo-butyl, 2-cyclopropyl-2-oxo-ethyl.

In case the optionally substituted alkyl group representing R¹⁴,including the examples of groups listed afore which can represent R¹⁴,contains a chiral carbon atom, the compound of the formula I can bepresent with respect to this carbon atom in any of it stereoisomericforms, i.e. in R configuration or in S configuration, or in the form ofa mixture of the stereoisomeric forms in any ratio, for example as amixture of the two stereoisomeric forms in a molar ratio of 1:1, asapplies to all chiral carbon atoms in the compounds of the formula I. Inone embodiment of the invention, the compound of the formula I has at achiral carbon atom in R¹⁴ pure stereochemical configuration, either Rconfiguration or S configuration, or essentially pure stereochemicalconfiguration, for example with a molar ratio of the two configurationsof 99:1 or greater.

In one embodiment of the invention, the (C₁-C₆)-alkyl group representingthe group R¹⁵ is a (C₁-C₄)-alkyl group, in another embodiment a(C₁-C₂)-alkyl group, in another embodiment a methyl group, wherein allthese alkyl groups are optionally substituted by one or more identicalor different substituents as indicated with respect to the compounds offormula I in general or in any embodiment specified above or below. Inone embodiment of the invention, the number of optional substituents inan alkyl group representing R¹⁵ is one or two, in another embodimentone. In one embodiment, the alkyl group representing R¹⁵ isunsubstituted. In one embodiment, the substituents which are optionallypresent on an alkyl group representing R¹⁵ are chosen from the seriesconsisting of HO— and (C₁-C₄)-alkyl-O—.

In one embodiment of the invention, the (C₁-C₆)-alkyl group representingthe group R¹⁶ is a (C₁-C₄)-alkyl group, in another embodiment a(C₁-C₃)-alkyl group, in another embodiment a (C₂-C₃)-alkyl group, inanother embodiment an ethyl group, in another embodiment a methyl group,wherein all these alkyl groups are optionally substituted by one or moreidentical or different substituents as indicated with respect to thecompounds of formula I in general or in any embodiment specified aboveor below. In one embodiment of the invention, the number of optionalsubstituents in an alkyl group representing R¹⁶ is one or two, inanother embodiment one. In one embodiment, an alkyl group representingR¹⁴ is unsubstituted, in another embodiment it is substituted by one ortwo identical or different substituents, in another embodiment it issubstituted by one substituent. In one embodiment, the substituentswhich are optionally present on an alkyl group representing R¹⁵ arechosen from the series consisting of HO— and (C₁-C₄)-alkyl-O—, inanother embodiment they are HO— substituents, in another embodiment theyare (C₁-C₄)-alkyl-O— substituents, and in another embodiment they are(C₁-C₂)-alkyl-O— substituents.

In one embodiment of the invention, the group R³⁰ is chosen from theseries consisting of R³¹, (C₃-C₇)-cycloalkyl and Het³—C_(u)H_(2u)—, inanother embodiment from the series consisting of (C₃-C₇)-cycloalkyl,R³²—C_(u)H_(2u)— and Het³—C_(u)H_(2u)—, in another embodiment from theseries consisting of R³²—C_(u)H_(2u)— and Het³—C_(u)H_(2u)—, in anotherembodiment R³⁰ is R³²—C_(u)H_(2u)—, and in another embodiment R³⁰ isR³¹. In one embodiment, u is an integer chosen from the seriesconsisting of 0, 1 and 2, in another embodiment from the seriesconsisting of 0 and 1, in another embodiment from the series consistingof 1 and 2, in another embodiment u is 0, and in another embodiment uis 1. In one embodiment, R³⁰ is R³²—C_(u)H_(2u)— and u is 0, i.e., inthis embodiment R³⁰ is chosen from the series consisting of phenyl andan aromatic 5-membered or 6-membered monocyclic heterocycle whichcomprises one, two or three identical or different ring heteroatomschosen from the series consisting of nitrogen, oxygen and sulfur and isbonded via a ring carbon atom, wherein the phenyl and the heterocycleall are optionally substituted as indicated with respect to thecompounds of formula I in general or in any embodiment specified aboveor below. In one embodiment, the divalent alkanediyl group C_(u)H_(2u)is a linear group.

In one embodiment, the (C₃-C₇)-cycloalkyl group representing R³⁰ is a(C₃-C₆)-cycloalkyl group, in another embodiment a (C₅-C₆)-cycloalkylgroup, in another embodiment a cyclopropyl group. In one embodiment, agroup Het³ occurring in R³⁰ is a saturated 4-membered to 6-memberedmonocyclic heterocycle, in another embodiment a saturated 5-membered or6-membered heterocycle, in another embodiment a saturated 6-memberedheterocycle, which comprises one or two identical or different ringheteroatoms, and in another embodiment comprises one ring heteroatom,which are chosen from the series consisting of nitrogen, oxygen andsulfur, and is bonded via a ring carbon atom and is optionallysubstituted as indicated with respect to the compounds of formula I ingeneral or in any embodiment specified above or below. In oneembodiment, the ring heteroatoms in a group Het³ occurring in R³⁰ arechosen from the series consisting of nitrogen and oxygen, in anotherembodiment from the series consisting of oxygen and sulfur, in anotherembodiment they are nitrogen atoms, and in another embodiment they areoxygen atoms. In one embodiment, the number of substituents which areoptionally present on a group Het³ occurring in R³⁰ is one, two, threeor four, in another embodiment one, two or three, in another embodimentone or two, in another embodiment one, and in another embodiment a groupHet³ occurring in R³⁰ is unsubstituted. In one embodiment, thesubstituents which are optionally present on a group Het³ occurring inR³⁰ are chosen from the series consisting of fluorine and (C₁-C₄)-alkyl,in another embodiment they are (C₁-C₄)-alkyl substituents.

In one embodiment of the invention, the (C₁-C₁₀-alkyl group representingR³¹ is a (C₁-C₈)-alkyl group, in another embodiment a (C₁-C₄)-alkylgroup, in another embodiment a (C₁-C₃)-alkyl group, in anotherembodiment a (C₁-C₂)-alkyl group, in another embodiment a methyl group,in another embodiment a (C₄-C₈)-alkyl group, in another embodiment a(C₅-C₈)-alkyl group, wherein all these alkyl groups are optionallysubstituted by one or more identical or different substituents asindicated with respect to the compounds of formula I in general or inany embodiment specified above or below. In one embodiment of theinvention, the number of optional substituents in an alkyl grouprepresenting R³¹ is one, two or three, in another embodiment one or two,in another embodiment one. In one embodiment, an alkyl grouprepresenting R³¹ is unsubstituted, and in another embodiment it issubstituted by one, two or three, in another embodiment by one or two,in another embodiment by one substituent as indicated. In oneembodiment, the optional substituents on an alkyl group representing R³¹are chosen from the series consisting of halogen, (C₃-C₇)-cycloalkyl,(C₁-C₈)-alkyl-O— and NC—, in another embodiment from the seriesconsisting of halogen, (C₃-C₇)-cycloalkyl and (C₁-C₈)-alkyl-O—, inanother embodiment from the series consisting of halogen and(C₃-C₇)-cycloalkyl, and in another embodiment they are(C₃-C₇)-cycloalkyl substituents. In one embodiment, halogen atomsoccurring as substituents on an alkyl group representing R³¹, are chosenfrom the series consisting of fluorine and chlorine atoms, and inanother embodiment they are fluorine atoms and, besides beingsubstituted by an other substituents, in this latter embodiment an alkylgroup representing R³¹ is thus optionally substituted by fluorinesubstituents as applies to alkyl groups in the compounds of the formulaI in general. In one embodiment, a (C₃-C₇)-cycloalkyl group occurring asa substituent on an alkyl group representing R³⁰ is a (C₃-C₆)-cycloalkylgroup, in another embodiment a (C₅-C₆)-cycloalkyl group, in anotherembodiment a cyclopropyl group.

In one embodiment of the invention, the group R³² is chosen from theseries consisting of phenyl and an aromatic 5-membered or 6-memberedmonocyclic heterocycle which comprises one or two identical or differentring heteroatoms, in another embodiment one ring heteroatom, which arechosen from the series consisting of nitrogen, oxygen and sulfur, and isbonded via a ring carbon atom, in another embodiment from the seriesconsisting of phenyl and an aromatic 6-membered monocyclic heterocyclewhich comprises one or two nitrogen atoms as ring heteroatoms, whereinthe phenyl and the heterocycle all are optionally substituted by one ormore identical or different substituents as indicated with respect tothe compounds of formula I in general or in any embodiment specifiedabove or below. In one embodiment, the ring heteroatoms in an aromaticheterocycle representing R³² are chosen from the series consisting ofnitrogen and sulfur, in another embodiment they are nitrogen atoms. Inone embodiment, R³² is chosen from the series consisting of phenyl andan aromatic 6-membered heterocycle as defined, in another embodiment R³²is a 6-membered monocyclic heterocycle as defined, in another embodimentR³² is chosen from the series consisting of phenyl, thiophenyl andpyridinyl, in another embodiment from the series consisting of phenyland pyridinyl, in another embodiment R³² is phenyl, and in anotherembodiment R³² is pyridinyl, all of which are optionally substituted byone or more identical or different substituents as indicated withrespect to the compounds of formula I in general or in any embodimentspecified above or below. In one embodiment, the number of substituentswhich are optionally present on a phenyl group and an aromaticheterocycle representing R³² is one, two, three or four, in anotherembodiment one, two or three, in another embodiment one or two, inanother embodiment one.

In one embodiment, the substituents which are optionally present on aphenyl group and an aromatic heterocycle representing R³², in particularon a phenyl group, are chosen from the series the series consisting offrom halogen, (C₁-C₆)-alkyl, (C₃-C₇)-cycloalkyl, R³³, (C₁-C₆)-alkyl-O—,R³³—O—, R³³—(C₁-C₄)-alkyl-O—, —O—CH₂—O—, —O—CF₂—O—,(C₁-C₆)-alkyl-S(O)_(m)—, H₂N—S(O)₂—, (C₁-C₄)-alkyl-NH—S(O)₂—,di((C₁-C₄)-alkyl)N—S(O)₂—, (C₁-C₆)-alkyl-NH—, di((C₁-C₆)-alkyl)N—, Het¹,(C₁-C₄)-alkyl-C(O)—NH—, Ar—C(O)—NH—, (C₁-C₄)-alkyl-S(O)₂—NH— and NC—, inanother embodiment from the series consisting of halogen, (C₁-C₆)-alkyl,(C₃-C₇)-cycloalkyl, R³³, (C₁-C₆)-alkyl-O—, R³³—O—, R³³—(C₁-C₄)-alkyl-O—,—O—CH₂—O—, —O—CF₂—O—, (C₁-C₆)-alkyl-S(O)_(m)—, H₂N—S(O)₂—,(C₁-C₄)-alkyl-NH—S(O)₂—, di((C₁-C₄)-alkyl)N—S(O)₂—, (C₁-C₆)-alkyl-NH—,di((C₁-C₆)-alkyl)N—, Het¹ and NC—, in another embodiment from the seriesconsisting of halogen, (C₁-C₆)-alkyl, (C₃-C₇)-cycloalkyl, R³³,(C₁-C₆)-alkyl-O—, R³³—O—, R³³—(C₁-C₄)-alkyl-O—, —O—CH₂—O—, —O—CF₂—O—,(C₁-C₆)-alkyl-S(O)_(m)—, (C₁-C₆)-alkyl-NH—, di((C₁-C₆)-alkyl)N—, Het¹and NC—, in another embodiment from the series consisting of halogen,(C₁-C₆)-alkyl, R³³, (C₁-C₆)-alkyl-O—, R³³—O—, —O—CH₂—O—, —O—CF₂—O—,(C₁-C₆)-alkyl-S(O)_(m)—, Het¹ and NC—, in another embodiment from theseries consisting of halogen, (C₁-C₆)-alkyl, R³³, (C₁-C₆)-alkyl-O—,R³³—O—, —O—CH₂—O—, —O—CF₂—O— and NC—, in another embodiment from theseries consisting of halogen, (C₁-C₆)-alkyl, R³³, (C₁-C₆)-alkyl-O—,R³³—O— and NC—, in another embodiment from the series consisting ofhalogen, (C₁-C₆)-alkyl, (C₃-C₇)-cycloalkyl, R³³, (C₁-C₆)-alkyl-O—,R³³—O—, R³³—(C₁-C₄)-alkyl-O—, —O—CH₂—O—, —O—CF₂—O—,(C₁-C₆)-alkyl-S(O)_(m)—, di((C₁-C₄)-alkyl)N—S(O)₂—, H₂N—,di((C₁-C₆)-alkyl)N—, Het¹, (C₁-C₄)-alkyl-C(O)—NH—, Ar—C(O)—NH— and NC—,in another embodiment from the series consisting of halogen,(C₁-C₆)-alkyl, (C₃-C₇)-cycloalkyl, R³³, (C₁-C₆)-alkyl-O—, R³³—O—,R³³—(C₁-C₄)-alkyl-O—, —O—CH₂—O—, —O—CF₂—O—, (C₁-C₆)-alkyl-S(O)_(m)—,di((C₁-C₄)-alkyl)N—S(O)₂—, H₂N—, di((C₁-C₆)-alkyl)N—, Het¹ and NC—, inanother embodiment from the series consisting of halogen, (C₁-C₆)-alkyl,(C₃-C₇)-cycloalkyl, R³³, (C₁-C₆)-alkyl-O—, R³³—O—, R³³—(C₁-C₄)-alkyl-O—,—O—CH₂—O—, —O—CF₂—O—, (C₁-C₆)-alkyl-S(O)_(m)—,di((C₁-C₄)-alkyl)N—S(O)₂—, di((C₁-C₆)-alkyl)N—, Het¹ and NC—, in anotherembodiment from the series consisting of halogen, (C₁-C₆)-alkyl,(C₃-C₇)-cycloalkyl, R³³, (C₁-C₆)-alkyl-O—, R³³—O—, R³³—(C₁-C₄)-alkyl-O—,(C₁-C₆)-alkyl-S(O)_(m)—, di((C₁-C₄)-alkyl)N—S(O)₂—, di((C₁-C₆)-alkyl)N—,Het¹ and NC—, in another embodiment from the series consisting ofhalogen, (C₁-C₆)-alkyl, R³³, (C₁-C₆)-alkyl-O— and R³³—O—, in anotherembodiment from the series consisting of halogen, (C₁-C₆)-alkyl, R³³ and(C₁-C₆)-alkyl-O—, in another embodiment from the series consisting ofhalogen, (C₁-C₆)-alkyl and R³³, in another embodiment from the seriesconsisting of halogen and (C₁-C₆)-alkyl. In one embodiment, in case thatsubstituents from the series consisting of (C₃-C₇)-cycloalkyl, R³³,R³³—O—, R³³—(C₁-C₄)-alkyl-O—, —O—CH₂—O—, —O—CF₂—O—, Het¹ and Ar—C(O)—NH—are present on a phenyl group and an aromatic heterocycle representingR³², not more than two such substituents, in another embodiment not morethan one such substituent, are present, either without any othersubstituents or together with any other substituents.

In one embodiment, a (C₁-C₆)-alkyl group occurring in a substituent on aphenyl group and an aromatic heterocycle representing R³² is a(C₁-C₄)-alkyl group, in another embodiment a (C₁-C₃)-alkyl group, inanother embodiment a (C₁-C₂)-alkyl group, in another embodiment a methylgroup. In one embodiment, a (C₃-C₇)-cycloalkyl group occurring as asubstituent on a phenyl group and an aromatic heterocycle representingR³² is a (C₃-C₆)-cycloalkyl group, in another embodiment a(C₃-C₅)-cycloalkyl group, in another embodiment a (C₃-C₄)-cycloalkylgroup, in another embodiment it is a cyclopropyl group. In oneembodiment, a group Ar occurring in a substituent on a phenyl group andan aromatic heterocycle representing R³² is chosen from the seriesconsisting of phenyl and an aromatic 5-membered or 6-memberedheterocycle which comprises one or two identical or different ringheteroatoms, in another embodiment one ring heteroatom, chosen from theseries consisting of nitrogen, oxygen and sulfur, which is bonded via aring carbon atom, and in another embodiment it is a phenyl group, whichgroups all are optionally substituted as indicated with respect to thecompounds of formula I in general or in any embodiment specified aboveor below. In one embodiment, the number of optional substituents on agroup Ar occurring in a substituent on a phenyl group and an aromaticheterocycle representing R³² is one or two, in another embodiment one,and the optional substituents are chosen from the series consisting ofhalogen, (C₁-C₄)-alkyl, (C₁-C₄)-alkyl-O—, (C₁-C₄)-alkyl-S(O)_(m)— andNC—, in another embodiment from the series consisting of halogen,(C₁-C₄)-alkyl and (C₁-C₄)-alkyl-O—, in another embodiment from theseries consisting of halogen and (C₁-C₄)-alkyl, and in anotherembodiment such a group Ar is unsubstituted.

In one embodiment, a group Het¹ occurring as a substituent on a phenylgroup or an aromatic heterocycle representing R³² is a saturated orunsaturated 4-membered to 6-membered monocyclic heterocycle, in anotherembodiment a 5-membered or 6-membered heterocycle, which comprises aring nitrogen atom via which Het¹ is bonded and optionally one or twofurther ring heteroatoms, in another embodiment one further ringheteroatom, which are chosen from the series consisting of nitrogen,oxygen and sulfur, which is optionally substituted as indicated withrespect to the compounds of formula I in general or in any embodimentspecified above or below. In one embodiment, a group Het¹ occurring as asubstituent on a phenyl group or an aromatic heterocycle representingR³² does not comprise any further ring heteroatom besides the ringnitrogen atom via which Het¹ is bonded. In one embodiment, a group Het¹occurring as a substituent on a phenyl group or an aromatic heterocyclerepresenting R³² is saturated, in another embodiment it is unsaturated.In one embodiment, the number of substituents which are optionallypresent on a group Het¹ occurring as a substituent on a phenyl group oran aromatic heterocycle representing R³² is one, two, three or four, inanother embodiment one, two or three, in another embodiment one or two,in another embodiment one, and in another embodiment such a group Het¹is unsubstituted. In one embodiment, the substituents which areoptionally present on a group Het¹ occurring as a substituent on aphenyl group or an aromatic heterocycle representing R³² are chosen fromthe series consisting of halogen, (C₁-C₄)-alkyl, HO—, (C₁-C₄)-alkyl-O—and oxo, in another embodiment from the series consisting of fluorine,(C₁-C₄)-alkyl, HO— and oxo, in another embodiment from the seriesconsisting of fluorine, (C₁-C₄)-alkyl and oxo, and in another embodimentthey are (C₁-C₄)-alkyl substituents.

Examples of groups R³² from any one or more of which R³² is chosen inone embodiment of the invention, are phenyl, 2-fluoro-phenyl,3-fluoro-phenyl, 4-fluoro-phenyl, 2-chloro-phenyl, 3-chloro-phenyl,4-chloro-phenyl, 3-bromo-phenyl, 4-bromo-phenyl, 2,3-dichloro-phenyl,2,4-dichloro-phenyl, 2,5-dichloro-phenyl, 2,6-dichloro-phenyl,3,4-dichloro-phenyl, 2,3-difluoro-phenyl, 2,4-difluoro-phenyl,2,5-difluoro-phenyl, 2,6-difluoro-phenyl, 3,4-difluoro-phenyl,2-chloro-6-fluoro-phenyl, 3,4,5-trifluoro-phenyl, 2-methyl-phenyl(o-tolyl), 3-methyl-phenyl (m-tolyl), 4-methyl-phenyl (p-tolyl),2,3-dimethyl-phenyl, 2,4-dimethyl-phenyl, 2,5-dimethyl-phenyl,2,6-dimethyl-phenyl, 3,4-dimethyl-phenyl, 2-ethyl-phenyl,3-ethyl-phenyl, 4-ethyl-phenyl, 3-isopropyl-phenyl, 3-tert-butyl-phenyl,4-tert-butyl-phenyl, 3-trifluoromethyl-phenyl, 4-trifluoromethyl-phenyl,2-fluoro-5-methyl-phenyl, 3-chloro-2-methyl-phenyl,5-chloro-2-methyl-phenyl, 5-chloro-2-fluoro-3-methyl-phenyl,2-fluoro-3-trifluoromethyl-phenyl, 2-fluoro-5-trifluoromethyl-phenyl,4-fluoro-3-trifluoromethyl-phenyl, 5-fluoro-3-trifluoromethyl-phenyl,3-chloro-4-trifluoromethyl-phenyl, 5-chloro-2-trifluoromethyl-phenyl,5-chloro-3-trifluoromethyl-phenyl, 2-methoxy-phenyl, 3-methoxy-phenyl,4-methoxy-phenyl, 3-ethoxy-phenyl, 3-propoxy-phenyl,3-isopropoxy-phenyl, 4-tert-butoxy-phenyl, 3-trifluoromethoxy-phenyl,4-trifluoromethoxy-phenyl, 3-(2,2,2-trifluoroethoxy)-phenyl,5-chloro-2-methoxy-phenyl, 3-chloro-4-methoxy-phenyl,5-fluoro-3-isopropoxy-phenyl, 2-fluoro-3-trifluoromethoxy-phenyl,4-methoxy-3,5-dimethyl-phenyl, 3-methoxy-5-trifluoromethyl-phenyl,2,3-methylenedioxy-phenyl, 2,3-difluoromethylenedioxy-phenyl,3,4-methylenedioxy-phenyl, 3,4-difluoromethylenedioxy-phenyl,3-methylsulfanyl-phenyl, 3-ethylsulfanyl-phenyl,3-trifluoromethylsulfanyl-phenyl, 3-methanesulfonyl-phenyl,3-ethanesulfonyl-phenyl, 3-sulfamoyl-phenyl, 2-cyano-phenyl,3-cyano-phenyl, 4-cyano-phenyl, thiophen-2-yl, thiophen-3-yl,3-chloro-thiophen-2-yl, 4-chloro-thiophen-2-yl, 5-chloro-thiophen-2-yl,4,5-dichloro-thiophen-2-yl, 5-chloro-thiophen-3-yl,2,5-dichloro-thiophen-3-yl, 4-methyl-thiophen-2-yl,5-methyl-thiophen-3-yl, 4,5-dimethyl-thiophen-2-yl, pyridin-2-yl,pyridin-3-yl, pyridin-4-yl, 2-chloro-pyridin-3-yl,5-chloro-pyridin-2-yl, 6-chloro-pyridin-3-yl, 2-chloro-pyridin-4-yl,2,6-dichloro-pyridin-3-yl, 6-methoxy-pyridin-3-yl,2-chloro-6-methoxy-pyridin-3-yl.

In one embodiment of the invention, the group R³³ is chosen from theseries consisting of phenyl and an aromatic 5-membered or 6-memberedmonocyclic heterocycle which comprises one or two identical or differentring heteroatoms, in another embodiment one ring heteroatom, which ischosen from the series consisting of nitrogen, oxygen and sulfur, and isbonded via a ring carbon atom, wherein the phenyl and the heterocycleall are optionally substituted by one or more identical or differentsubstituents as indicated with respect to the compounds of formula I ingeneral or in any embodiment specified above or below. In oneembodiment, the ring heteroatoms in an aromatic heterocycle representingR³³ are chosen from the series consisting of nitrogen and sulfur, inanother embodiment they are nitrogen atoms. In one embodiment, R³³ ischosen from the series consisting of phenyl and an aromatic 6-memberedheterocycle as defined, in another embodiment from the series consistingof phenyl and an aromatic 6-membered heterocycle which comprises one ortwo nitrogen atoms as ring heteroatoms, in another embodiment R³³ is a6-membered monocyclic heterocycle as defined, in another embodiment itis an aromatic 6-membered heterocycle which comprises one or twonitrogen atoms as ring heteroatoms, in another embodiment R³³ is chosenfrom the series consisting of phenyl, thiophenyl and pyridinyl, inanother embodiment from the series consisting of phenyl and pyridinyl,in another embodiment R³³ is phenyl, and in another embodiment R³³ ispyridinyl, all of which are optionally substituted by one or moreidentical or different substituents as indicated with respect to thecompounds of formula I in general or in any embodiment specified aboveor below. In one embodiment, the number of substituents which areoptionally present on a phenyl group and an aromatic heterocyclerepresenting R³³ is one, two or three, in another embodiment one or two,in another embodiment one.

In one embodiment, the substituents which are optionally present on aphenyl group and an aromatic heterocycle representing R³³, are chosenfrom the series consisting of halogen, (C₁-C₆)-alkyl,(C₃-C₇)-cycloalkyl, HO—, (C₁-C₆)-alkyl-O—, (C₁-C₆)-alkyl-S(O)_(m)—,H₂N—S(O)₂—, di((C₁-C₄)-alkyl)N—S(O)₂— and NC—, in another embodimentfrom the series consisting of halogen, (C₁-C₆)-alkyl,(C₃-C₇)-cycloalkyl, HO—, (C₁-C₆)-alkyl-O—, H₂N—S(O)₂—,di((C₁-C₄)-alkyl)N—S(O)₂— and NC—, in another embodiment from the seriesconsisting of halogen, (C₁-C₆)-alkyl, (C₃-C₇)-cycloalkyl, HO—,(C₁-C₆)-alkyl-O— and NC—, are chosen from the series the seriesconsisting of halogen, (C₁-C₄)-alkyl, (C₁-C₄)-alkyl-O—,(C₁-C₄)-alkyl-S(O)_(m)— and NC—, in another embodiment from the seriesconsisting of halogen, (C₁-C₄)-alkyl, (C₁-C₄)-alkyl-O— and NC—, inanother embodiment from the series consisting of halogen, (C₁-C₄)-alkyland (C₁-C₄)-alkyl-O—, in another embodiment from the series consistingof halogen and (C₁-C₄)-alkyl. In one embodiment, a (C₁-C₆)-alkyl groupoccurring in a substituent on a phenyl group and an aromatic heterocyclerepresenting R³³ is a (C₁-C₄)-alkyl group, in another embodiment a(C₁-C₃)-alkyl group, in another embodiment a (C₁-C₂)-alkyl group, inanother embodiment a methyl group. In one embodiment, a(C₃-C₇)-cycloalkyl group occurring as a substituent on a phenyl groupand an aromatic heterocycle representing R³² is a (C₃-C₆)-cycloalkylgroup, in another embodiment a (C₃-C₅)-cycloalkyl group, in anotherembodiment a (C₃-C₄)-cycloalkyl group, in another embodiment it is acyclopropyl group.

In one embodiment of the invention, the group R⁴⁰ is chosen from theseries consisting of hydrogen and (C₁-C₂)-alkyl, in another embodimentfrom the series consisting of hydrogen and methyl, and in anotherembodiment R⁴⁰ is hydrogen. In case R³⁰ and R⁴⁰ are different and thecarbon atom carrying R³⁰ and R⁴⁰ thus is chiral, in one embodiment ofthe invention the compound of the formula I has at this carbon atom purestereochemical configuration, either R configuration or S configuration,or essentially pure stereochemical configuration, for example with amolar ratio of the two configurations of 99:1 or greater. In case R³⁰ isR³²—C_(u)H_(2u)— and u is 0, i.e. R³⁰ is phenyl or an aromaticheterocycle as defined, R⁴⁰ is hydrogen and R⁵⁰ is hydrogen, in oneembodiment of the invention the compound of the formula I has at thecarbon atom carrying R³⁰ and R⁴⁰ pure S configuration, or essentiallypure S configuration, for example with a molar ratio of S configurationto R configuration of 99:1 or greater.

In case R³⁰ and R⁴⁰ together are a divalent group (CH₂)_(x), the twogroups R³⁰ and R⁴⁰ together with the carbon atom carrying them form acycloalkane ring chosen from cyclopropane, cyclobutane, cyclopentane andcyclohexane, which carries the moieties —C(O)—NH and —C(R⁵⁰)(R⁶⁰)-Gdepicted in formula I on the same ring carbon atom. In one embodiment ofthe invention, the number of (C₁-C₄)-alkyl substituents which areoptionally present on the group (CH₂)_(x), is one, two, three or four,in another embodiment one or two, and in another embodiment no alkylsubstituents are present on the group (CH₂)_(x). In one embodiment, a(C₁-C₄)-alkyl group occurring as a substituent on the group (CH₂)_(x) isa methyl group. In one embodiment, the integer x is chosen from theseries consisting of 2, 4 and 5, in another embodiment from 4 and 5, inanother embodiment x is 2, and in another embodiment x is 4. In oneembodiment of the invention, R³⁰ and R⁴⁰ together cannot be (CH₂)_(x),and in this embodiment R³⁰ and R⁴⁰ thus only have their other meaningsas defined.

In one embodiment of the invention, the group R⁵⁰ is chosen from theseries consisting of hydrogen, (C₁-C₄)-alkyl and HO—, in anotherembodiment from the series consisting of hydrogen and (C₁-C₄)-alkyl, inanother embodiment from the series consisting of hydrogen and(C₁-C₂)-alkyl, in another embodiment from the series consisting ofhydrogen and methyl, in another embodiment from the series consisting ofhydrogen and HO—, and in another embodiment R⁵⁰ is hydrogen.

In one embodiment of the invention, the group R⁶⁰ is chosen from theseries consisting of hydrogen and (C₁-C₄)-alkyl, in another embodimentfrom the series consisting of hydrogen and (C₁-C₃)-alkyl, in anotherembodiment from the series consisting of hydrogen and (C₁-C₂)-alkyl, inanother embodiment from the series consisting of hydrogen and methyl,and in another embodiment R⁶⁰ is hydrogen. In one embodiment of theinvention, R⁵⁰ and R⁶⁰ both are hydrogen. In case R⁵⁰ and R⁶⁰ aredifferent and the carbon atom carrying R⁵⁰ and R⁶⁰ thus is chiral, inone embodiment of the invention the compound of the formula I has atthis carbon atom pure stereochemical configuration, either Rconfiguration or S configuration, or essentially pure stereochemicalconfiguration, for example with a molar ratio of the two configurationsof 99:1 or greater.

In case R⁵⁰ and R⁶⁰ together are a divalent group (CH₂)_(y), the twogroups R⁵⁰ and R⁶⁰ together with the carbon atom carrying them form acycloalkane ring chosen from cyclopropane, cyclobutane, cyclopentane andcyclohexane, which carries the moieties —C(R³⁰)(R⁴⁰)— and G depicted informula I on the same ring carbon atom. In one embodiment of theinvention, the number of (C₁-C₄)-alkyl substituents which are optionallypresent on the group (CH₂)_(y), is one, two, three or four, in anotherembodiment one or two, and in another embodiment no alkyl substituentsare present on the group (CH₂)_(y). In one embodiment, a (C₁-C₄)-alkylgroup occurring as a substituent on the group (CH₂)_(y) is a methylgroup. In one embodiment, the integer y is chosen from the seriesconsisting of 2, 4 and 5, in another embodiment from 4 and 5, in anotherembodiment y is 2, and in another embodiment y is 4. In one embodimentof the invention, R⁵⁰ and R⁶⁰ together cannot be (CH₂)_(y), and in thisembodiment R⁵⁰ and R⁶⁰ thus only have their other meanings as defined.In one embodiment of the invention, R⁵⁰ and R⁶⁰ together cannot be(CH₂)_(y) if simultaneously R³⁰ and R⁴⁰ together are (CH₂)_(x).

In one embodiment of the invention, the group R⁷¹ is chosen from theseries consisting of hydrogen and (C₁-C₆)-alkyl, in another embodimentfrom the series consisting of hydrogen and (C₁-C₄)-alkyl, in anotherembodiment from the series consisting of hydrogen and (C₁-C₃)-alkyl, inanother embodiment from the series consisting of hydrogen and(C₁-C₂)-alkyl, in another embodiment R⁷¹ is hydrogen, in anotherembodiment R⁷¹ is (C₁-C₆)-alkyl, in another embodiment R⁷¹ is(C₁-C₄)-alkyl, in another embodiment R⁷¹ is (C₁-C₃)-alkyl, and inanother embodiment R⁷¹ is (C₁-C₂)-alkyl, wherein all these alkyl groupsare optionally substituted as indicated with respect to the compounds offormula I in general or in any embodiment specified above or below. Inone embodiment, the number of substituents which are optionally presenton an alkyl group representing R⁷¹ is one or two, in another embodimentit is one, in another embodiment an alkyl group representing R⁷¹ isunsubstituted. In one embodiment, substituents which are optionallypresent on an alkyl group representing R⁷¹ are (C₁-C₆)-alkyl-O—substituents, in another embodiment (C₁-C₄)-alkyl-O— substituents, inanother embodiment (C₁-C₃)-alkyl-O— substituents, in another embodiment(C₁-C₆)-alkyl-C(O)—O— substituents, in another embodiment(C₁-C₄)-alkyl-C(O)—O— substituents, in another embodiment(C₁-C₃)-alkyl-C(O)—O— substituents.

In one embodiment the group R⁷² is chosen from the series consisting ofhydrogen, (C₁-C₆)-alkyl, (C₃-C₆)-cycloalkyl—CH₂—(CH₂)_(b)—(C₃-C₆)-cycloalkyl and —(CH₂)_(b)—Het⁴, where alkyl orcycloalkyl is optionally substituted by one or more identical ordifferent substituents chosen from the series consisting of halogen,HO—, HOOC—, (C₁-C₆)-alkyl-O— and (C₁-C₆)-alkyl-C(O)—O—, NC—,N((C₁-C₄)-alkyl)₂ and b is 0, 1 or 2 and the group R⁷³ is chosen fromthe series consisting hydrogen, (C₁-C₆)-alkyl.

In another embodiment the groups R⁷² and R⁷³ together with the nitrogenatom to which they are bonded form a saturated 4-membered to 7-memberedmonocyclic heterocycle, which contain optionally one further ringheteroatom chosen from the series consisting of nitrogen, oxygen andsulfur, which is optionally substituted by one or more identical ordifferent substituents chosen from the series consisting of halogen,(C₁-C₄)-alkyl, HO— and (C₁-C₄)-alkyl-O—.

In another embodiment the group R⁷² is chosen from the series consistingof hydrogen, (C₁-C₆)-alkyl, (C₃-C₆)-cycloalkyl, Het⁴ and —CH₂—Het⁴,where alkyl or cycloalkyl is optionally substituted by one or moreidentical or different substituents chosen from the series consisting ofhalogen, HO—, HOOC—, (C₁-C₆)-alkyl-O— and (C₁-C₆)-alkyl-C(O)—O—, NC—,N((C₁-C₄)-alkyl)₂ and the group R⁷³ is chosen from the series consistinghydrogen, (C₁-C₆)-alkyl.

In another embodiment the groups R⁷² and R⁷³ together with the nitrogenatom to which they are bonded form a saturated 5-membered to 6-memberedmonocyclic heterocycle, which contain optionally one further ringheteroatom chosen from the series consisting of nitrogen, oxygen andsulfur, which is optionally substituted by one or more identical ordifferent substituents chosen from the series consisting of halogen,(C₁-C₄)-alkyl, HO— and (C₁-C₄)-alkyl-O—.

In one embodiment the group R⁷² is chosen from the series consisting ofhydrogen, (C₁-C₆)-alkyl, (C₃-C₆)-cycloalkyl and —CH₂—Het⁴, where alkylor cycloalkyl is optionally substituted by one or more identical ordifferent substituents chosen from the series consisting of halogen,HO—, HOOC—, (C₁-C₆)-alkyl-O— and (C₁-C₆)-alkyl-C(O)—O—, NC—,N((C₁-C₄)-alkyl)₂ and the group R⁷³ is chosen from the series consistinghydrogen and (C₁-C₆)-alkyl.

In another embodiment the groups R⁷² and R⁷³ together with the nitrogenatom to which they are bonded form a saturated 5-membered to 6-memberedmonocyclic heterocycle, which contain no further ring heteroatoms, whichis optionally substituted by one or more identical or differentsubstituents chosen from the series consisting of halogen,(C₁-C₄)-alkyl, HO— and (C₁-C₄)-alkyl-O—.

In one embodiment the group R⁷² is chosen from the series consisting ofhydrogen, 2,2-dimethyl-butane-3yl, 2,2-dimethyl-propane-3yl, pentan-3yl,propane-2yl, 2-methyl-propane-2yl, butane-1yl, butane-2yl,2-methyl-butane-3yl, 2-methyl-butane-2-yl, —CH₂CHF₂, —CHCF₃, CH₂CN,—CH₂CH₂OCH₃, —CH(CH₂OH)CH(CH₃)₂, —CH₂C(CH₃)₂—CH₂OH, CH(C₂H₅)CH₂OCH₃,CH₂CH₂CH₂N(CH₃)₂, cyclopropane, cyclobutane, cyclopentane, cyclohexaneand —CH₂—Het⁴ and the group R⁷³ is hydrogen. In another embodiment thegroups R⁷² and R⁷³ together with the nitrogen atom to which they arebonded form pyrrolidine, which is optionally substituted by HO—. Inanother embodiment the group R⁷² is chosen from the series consisting ofhydrogen, (C₁-C₆)-alkyl, where alkyl is substituted by one or more timesby HO— and the group R⁷³ is hydrogen.

In one embodiment of the invention, the groups R⁷² and R⁷³ areindependently of each other chosen from the series consisting ofhydrogen and (C₁-C₂)-alkyl, in another embodiment from the seriesconsisting of hydrogen and methyl. In one embodiment, one of the groupsR⁷² and R⁷³ is hydrogen and the other is chosen from the seriesconsisting of hydrogen and (C₁-C₄)-alkyl, in another embodiment from theseries consisting of hydrogen and (C₁-C₂)-alkyl, in another embodimentfrom the series consisting of hydrogen an methyl, and in anotherembodiment both groups R⁷² and R⁷³ are hydrogen.

In one embodiment of the invention the group Het⁴, independently of eachother group Het⁴, is a saturated or unsaturated 4-membered to 8-memberedmonocyclic heterocycle which comprises one to four ring heteroatomschosen from the series consisting of nitrogen, oxygen and sulfur whichis optionally substituted by one or more identical or differentsubstituents chosen from the series consisting of halogen,(C₁-C₄)-alkyl, HO—, (C₁-C₄)-alkyl-O—, oxo and NC—;

In another embodiment the group Het⁴, independently of each other groupHet⁴, is a saturated or unsaturated 5-membered to 6-membered monocyclicheterocycle which comprises one to four ring heteroatoms chosen from theseries consisting of nitrogen, oxygen and sulfur which is optionallysubstituted by one or more identical or different substituents chosenfrom the series consisting of halogen, (C₁-C₄)-alkyl, HO—,(C₁-C₄)-alkyl-O—, oxo and NC—;

In another embodiment the group Het⁴, independently of each other groupHet⁴, is a unsaturated 5-membered to 6-membered monocyclic heterocyclewhich comprises one to four ring heteroatoms chosen from the seriesconsisting of nitrogen, oxygen and sulfur which is optionallysubstituted by one or more identical or different substituents chosenfrom the series consisting of halogen, (C₁-C₄)-alkyl, HO—,(C₁-C₄)-alkyl-O— and NC—;

In another embodiment the group Het⁴, independently of each other groupHet⁴, is selected from 1,2-oxadiazolyl, tetrazlolyl, pyrazolyl, furanyl,pyridinyl, pyrizinyl, which is optionally substituted by methyl.

In one embodiment of the invention, a group Ar in any occurrence in thecompounds of the formula I, independently of each other group Ar, ischosen from the series consisting of phenyl and an aromatic 5-memberedor 6-membered monocyclic heterocycle which comprises one or twoidentical or different ring heteroatoms, in another embodiment one ringheteroatom, which is chosen from the series consisting of nitrogen,oxygen and sulfur, and which is bonded via a ring carbon atom, inanother embodiment Ar is chosen from the series consisting of phenyl andan aromatic 6-membered heterocycle which comprises one or two nitrogenatoms as ring heteroatoms, in another embodiment Ar is chosen from theseries consisting of phenyl, thiophenyl and pyridinyl, in anotherembodiment from the series consisting of phenyl and thiophenyl, inanother embodiment from the series consisting of phenyl and pyridinyl,in another embodiment a group Ar is phenyl, and in another embodiment agroup Ar is pyridinyl, wherein the phenyl and all heterocycles areoptionally substituted as indicated with respect to the compounds offormula I in general or in any embodiment specified above or below. Inone embodiment, the number of substituents which are optionally presenton a group Ar, independently of each other group Ar, is one, two, threeor four, in another embodiment one, two or three, in another embodimentone or two, in another embodiment one, and in another embodiment a groupAr is unsubstituted. In one embodiment, in case that substituents fromthe series consisting of —O—CH₂—O— and —O—CF₂—O— are present on a groupAr, not more than two such substituents, in another embodiment not morethan one such substituent, are present, either without any othersubstituents or together with any other substituents.

In one embodiment, the substituents which are optionally present on agroup Ar, independently of each other group Ar, are chosen from theseries consisting of halogen, (C₁-C₆)-alkyl, (C₁-C₆)-alkyl-O—,—O—CH₂—O—, —O—CF₂—O—, (C₁-C₆)-alkyl-S(O)_(m)— and NC—, in anotherembodiment from the series consisting of halogen, (C₁-C₆)-alkyl,(C₁-C₆)-alkyl-O—, (C₁-C₆)-alkyl-S(O)_(m)— and NC—, in another embodimentfrom the series consisting of halogen, (C₁-C₆)-alkyl, (C₁-C₆)-alkyl-O—and NC—, in another embodiment from the series consisting of halogen,(C₁-C₆)-alkyl and (C₁-C₆)-alkyl-O—, in another embodiment from theseries consisting of halogen, (C₁-C₄)-alkyl and (C₁-C₄)-alkyl-O—, inanother embodiment from the series consisting of halogen and(C₁-C₄)-alkyl.

A subject of the invention are all compounds of the formula I whereinany one or more structural elements such as groups, substituents andnumbers are defined as in any of the specified embodiments ordefinitions of the elements or have one or more of the specific meaningswhich are mentioned herein as examples of elements, wherein allcombinations of one or more specified embodiments and/or definitionsand/or specific meanings of the elements are a subject of the presentinvention. Also with respect to all such compounds of the formula I, alltheir stereoisomeric forms and mixtures of stereoisomeric forms in anyratios, and their physiologically acceptable salts, and thephysiologically acceptable solvates of any of them, are a subject of thepresent invention.

As an example of compounds of the invention which with respect to anystructural elements are defined as in specified embodiments of theinvention or definitions of such elements, compounds of the formula Imay be mentioned wherein

-   A is chosen from the series consisting of C(R¹) and N;-   D is chosen from the series consisting of N(R²), O and S;-   E is N;-   R¹ is chosen from the series consisting of hydrogen, halogen and    (C₁-C₄)-alkyl;-   R² is chosen from the series consisting of    (C₃-C₇)-cycloalkyl-C_(s)H_(2s)— and Ar—C_(s)H_(2s)—, wherein s is an    integer chosen from the series consisting of 0, 1 and 2;-   and all other groups and numbers are defined as in the general    definition of the compounds of the formula I or in any specified    embodiments of the invention or definitions of structural elements,    in any of their stereoisomeric forms or a mixture of stereoisomeric    forms in any ratio, and their physiologically acceptable salts, and    the physiologically acceptable solvates of any of them.

As another such example, compounds of the formula I may be mentioned,wherein

-   A is chosen from the series consisting of C(R¹) and N;-   D is N(R²);-   E is N;-   R¹ is chosen from the series consisting of hydrogen, halogen and    (C₁-C₄)-alkyl;-   R² is Ar—C_(s)H_(2s)—, wherein s is an integer chosen from the    series consisting of 0, 1 and 2;-   and all other groups and numbers are defined as in the general    definition of the compounds of the formula I or in any specified    embodiments of the invention or definitions of structural elements,    in any of their stereoisomeric forms or a mixture of stereoisomeric    forms in any ratio, and their physiologically acceptable salts, and    the physiologically acceptable solvates of any of them.

As another such example, compounds of the formula I may be mentioned,wherein

-   A is C(R¹);-   D is N(R²);-   E is N;-   R¹ is chosen from the series consisting of hydrogen, halogen and    (C₁-C₄)-alkyl;-   R² is Ar—C_(s)H_(2s)—, wherein s is 0;-   the group Ar in the group R², irrespective of the meaning of Ar in    other positions in the compounds of the formula I, is chosen from    the series consisting of phenyl and an aromatic 6-membered    heterocycle which comprises one or two nitrogen atoms as ring    heteroatoms, wherein the phenyl and the heterocycle are all    optionally substituted by one, two or three identical or different    substituents chosen from the series consisting of halogen,    (C₁-C₆)-alkyl, (C₁-C₆)-alkyl-O—, (C₁-C₆)-alkyl-S(O)_(m)— and NC—;-   and all other groups and numbers are defined as in the general    definition of the compounds of the formula I or in any specified    embodiments of the invention or definitions of structural elements,    in any of their stereoisomeric forms or a mixture of stereoisomeric    forms in any ratio, and their physiologically acceptable salts, and    the physiologically acceptable solvates of any of them.

As another such example, compounds of the formula I may be mentioned,wherein

-   R¹⁰ is R¹¹—O—;-   R¹¹ is chosen from the series consisting of hydrogen and R¹⁴;-   R¹⁴ is (C₁-C₈)-alkyl which is optionally substituted by one, two or    three identical or different substituents chosen from the series    consisting of HO—, R¹⁶—O—, oxo, (C₃-C₇)-cycloalkyl, Ar, Het¹ and    Het³;-   R¹⁶ is (C₁-C₆)-alkyl which is optionally substituted by one or two    identical or different substituents chosen from the series    consisting of HO— and (C₁-C₄)-alkyl-O—;-   and all other groups and numbers are defined as in the general    definition of the compounds of the formula I or in any specified    embodiments of the invention or definitions of structural elements,    in any of their stereoisomeric forms or a mixture of stereoisomeric    forms in any ratio, and their physiologically acceptable salts, and    the physiologically acceptable solvates of any of them.

As another such example, compounds of the formula I may be mentioned,wherein

-   G is chosen from the series consisting of R⁷¹—O—C(O)—and    R⁷²—N(R⁷³)—C(O)—;-   R³⁰ is R³²—C_(u)H_(2u)—, wherein u is an integer chosen from the    series consisting of 0 and 1;-   R³² is chosen from the series consisting of phenyl and an aromatic    6-membered monocyclic heterocycle which comprises one or two    nitrogen atoms as ring heteroatoms, wherein the phenyl and the    heterocycle all are optionally substituted by one, two or three    identical or different substituents chosen from the series    consisting of halogen, (C₁-C₆)-alkyl, (C₃-C₇)-cycloalkyl, R³³,    (C₁-C₆)-alkyl-O—, R³³—O—, R³³—(C₁-C₄)-alkyl-O—, —O—CH₂—O—,    —O—CF₂—O—, (C₁-C₆)-alkyl-S(O)_(m)—, (C₁-C₆)-alkyl-NH—,    di((C₁-C₆)-alkyl)N—, Het¹ and NC—;-   R³³ is chosen from the series consisting of phenyl and pyridinyl    which all are optionally substituted by one, two or three identical    or different substituents chosen from the series consisting of    halogen, (C₁-C₄)-alkyl, (C₁-C₄)-alkyl-O—, (C₁-C₄)-alkyl-S(O)_(m)—    and NC—;-   R⁴⁰ is hydrogen;-   R⁵⁰ is hydrogen;-   R⁶⁰ is hydrogen;-   and all other groups and numbers are defined as in the general    definition of the compounds of the formula I or in any specified    embodiments of the invention or definitions of structural elements,    in any of their stereoisomeric forms or a mixture of stereoisomeric    forms in any ratio, and their physiologically acceptable salts, and    the physiologically acceptable solvates of any of them.

As another such example, compounds of the formula I may be mentioned,wherein

-   A is chosen from the series consisting of C(R¹) and N;-   D is N(R²);-   E is chosen from the series consisting of C(R³) and N;-   G is chosen from the series consisting of R⁷¹—O—C(O)— and    R⁷²—N(R⁷³)—C(O)—;-   R¹ is chosen from the series consisting of hydrogen, halogen,    (C₁-C₆)-alkyl, HO— and (C₁-C₆)-alkyl-O—;-   R² is chosen from the series consisting of (C₁-C₇)-alkyl,    (C₃-C₇)-cycloalkyl-C_(s)H_(2s)— and Ar—C_(s)H_(2s)—, wherein s is an    integer chosen from the series consisting of 0, 1, 2 and 3;-   R³ is chosen from the series consisting of hydrogen, halogen,    (C₁-C₆)-alkyl and (C₁-C₆)-alkyl-O—;-   R¹⁰ is chosen from the series consisting of R¹¹—O—,    R¹²—N(R¹³)—C(O)—O— and Het²—C(O)—O—;-   R¹¹ is chosen from the series consisting of hydrogen, R¹⁴,    (C₃-C₇)-cycloalkyl and Het³;-   R¹² and R¹³ are independently of each other chosen from the series    consisting of hydrogen, R¹⁵ and Ar;-   R¹⁴ is (C₁₀-C₁₀)-alkyl which is optionally substituted by one or    more identical or different substituents chosen from the series    consisting of halogen, HO—, R¹⁶—O—, oxo, (C₃-C₇)-cycloalkyl, Ar,    Het¹, Het³, NC—, H₂N—C(O)—, (C₁-C₄)-alkyl-NH—C(O)—,    di((C₁-C₄)-alkyl)N—C(O)— and Het¹—C(O)—;-   R¹⁵ is (C₁-C₆)-alkyl;-   R¹⁶ is (C₁-C₆)-alkyl which is optionally substituted by one or more    identical or different substituents chosen from the series    consisting of HO— and (C₁-C₄)-alkyl-O—;-   R³⁰ is chosen from the series consisting of (C₃-C₇)-cycloalkyl,    R³²—C_(u)H_(2u)— and Het³—C_(u)H_(2u)—, wherein u is an integer    chosen from the series consisting of 0, 1, 2 and 3;-   R³² is chosen from the series consisting of phenyl and an aromatic    6-membered monocyclic heterocycle which comprises one or two    nitrogen atoms as ring heteroatoms, wherein the phenyl and the    heterocycle all are optionally substituted by one or more identical    or different substituents chosen from the series consisting of    halogen, (C₁-C₆)-alkyl, (C₃-C₇)-cycloalkyl, R³³, HO—,    (C₁-C₆)-alkyl-O—, R³³—O—, R³³—(C₁-C₄)-alkyl-O—, —O—CH₂—O—,    —O—CF₂—O—, (C₁-C₆)-alkyl-S(O)_(m)—, di((C₁-C₄)-alkyl)N—S(O)₂—, H₂N—,    di((C₁-C₆)-alkyl)N—, Het¹, (C₁-C₄)-alkyl-C(O)—NH—, Ar—C(O)—NH— and    NC—;-   R³³ is chosen from the series consisting of phenyl and an aromatic    6-membered monocyclic heterocycle which comprises one or two    nitrogen atoms as ring heteroatoms, wherein the phenyl and the    heterocycle all are optionally substituted by one or more identical    or different substituents chosen from the series consisting of    halogen, (C₁-C₆)-alkyl, (C₃-C₇)-cycloalkyl, HO—, (C₁-C₆)-alkyl-O—,    (C₁-C₆)-alkyl-S(O)_(m)—, H₂N—S(O)₂—, di((C₁-C₄)-alkyl)N—S(O)₂— and    NC—;-   R⁴⁰ is hydrogen;-   R⁵⁰ is chosen from the series consisting of hydrogen and HO—;-   R⁶⁰ is hydrogen;-   R⁷¹ is chosen from the series consisting of hydrogen and    (C₁-C₈)-alkyl which is optionally substituted by one or more    identical or different substituents chosen from the series    consisting (C₁-C₆)-alkyl-O— and (C₁-C₆)-alkyl-C(O)—O—;-   R⁷² and R⁷³ are independently of each other chosen from the series    consisting of hydrogen and (C₁-C₄)-alkyl;-   Ar, independently of each other group Ar, is chosen from the series    consisting of phenyl and an aromatic 5-membered or 6-membered    monocyclic heterocycle which comprises one, two or three identical    or different ring heteroatoms chosen from the series consisting of    nitrogen, oxygen and sulfur and is bonded via a ring carbon atom,    wherein the phenyl and the heterocycle all are optionally    substituted by one or more identical or different substituents    chosen from the series consisting of halogen, (C₁-C₆)-alkyl,    (C₁-C₆)-alkyl-O—, —O—CH₂—O—, —O—CF₂—O—, (C₁-C₆)-alkyl-S(O)_(m)— and    NC—;-   Het¹, independently of each other group Het¹, is a saturated or    unsaturated 4-membered to 8-membered monocyclic heterocycle which    comprises a ring nitrogen atom via which Het¹ is bonded and    optionally one or two identical or different further ring    heteroatoms chosen from the series consisting of nitrogen, oxygen    and sulfur, which is optionally substituted by one or more identical    or different substituents chosen from the series consisting of    halogen, (C₁-C₄)-alkyl, HO—, (C₁-C₄)-alkyl-O—, oxo and NC—;-   Het² is a saturated 4-membered to 7-membered monocyclic heterocycle    which comprises a ring nitrogen atom via which Het² is bonded and    optionally one further ring heteroatom chosen from the series    consisting of nitrogen, oxygen and sulfur, which is optionally    substituted by one or more identical or different substituents    chosen from the series consisting of halogen, (C₁-C₄)-alkyl, HO— and    (C₁-C₄)-alkyl-O—;-   Het³, independently of each other group Het³, is a saturated    4-membered to 7-membered monocyclic heterocycle which comprises one    or two identical or different ring heteroatoms chosen from the    series consisting of nitrogen, oxygen and sulfur and is bonded via a    ring carbon atom, which is optionally substituted by one or more    identical or different substituents chosen from the series    consisting of fluorine, (C₁-C₄)-alkyl and oxo;-   m, independently of each other number m, is an integer chosen from    the series consisting of 0, 1 and 2;-   wherein all cycloalkyl groups, independently of each other, are    optionally substituted by one or more identical or different    substituents chosen from the series consisting of fluorine and    (C₁-C₄)-alkyl;-   wherein all alkyl, C_(s)H_(2s), C_(u)H_(2u), (CH₂)_(x) and (CH₂)_(y)    groups, independently of each other, and independently of any other    substituents, are optionally substituted by one or more fluorine    substituents;-   in any of their stereoisomeric forms or a mixture of stereoisomeric    forms in any ratio, and their physiologically acceptable salts, and    the physiologically acceptable solvates of any of them.

As another such example, compounds of the formula I may be mentioned,wherein

-   A is C(R¹);-   D is N(R²);-   E is N;-   G is chosen from the series consisting of R⁷¹—O—C(O)— and    R⁷²—N(R⁷³)—C(O)—;-   R¹ is chosen from the series consisting of hydrogen, halogen and    (C₁-C₄)-alkyl;-   R² is Ar—C_(s)H_(2s)—, wherein s is 0;-   R¹⁰ is R¹¹—O—;-   R¹¹ is chosen from the series consisting of hydrogen and R¹⁴;-   R¹⁴ is (C₁-C₁₀)-alkyl which is optionally substituted by one, two or    three identical or different substituents chosen from the series    consisting of HO—, R¹⁶—O—, oxo, (C₃-C₇)-cycloalkyl, Ar, Het¹,    di((C₁-C₄)-alkyl)N— and Het¹—C(O)—;-   R¹⁶ is (C₁-C₆)-alkyl which is optionally substituted by one or two    identical or different substituents chosen from the series    consisting of HO— and (C₁-C₄)-alkyl-O—;-   R³⁰ is R³²—C_(u)H_(2u)—, wherein u is an integer chosen from the    series consisting of 0 and 1;-   R³² is chosen from the series consisting of phenyl and an aromatic    6-membered monocyclic heterocycle which comprises one or two    nitrogen atoms as ring heteroatoms, wherein the phenyl and the    heterocycle all are optionally substituted by one, two or three    identical or different substituents chosen from the series    consisting of halogen, (C₁-C₆)-alkyl, (C₃-C₇)-cycloalkyl, R³³,    (C₁-C₆)-alkyl-O—, R³³—O—, R³³—(C₁-C₄)-alkyl-O—, —O—CH₂—O—,    —O—CF₂—O—, (C₁-C₆)-alkyl-S(O)_(m)—, di((C₁-C₆)-alkyl)N—, Het¹ and    NC—;-   R³³ is chosen from the series consisting of phenyl and pyridinyl    which all are optionally substituted by one, two or three identical    or different substituents chosen from the series consisting of    halogen, (C₁-C₄)-alkyl, (C₁-C₄)-alkyl-O—, (C₁-C₄)-alkyl-S(O)_(m)—    and NC—;-   R⁴⁰ is hydrogen;-   R⁵⁰ is hydrogen;-   R⁶⁰ is hydrogen;-   R⁷¹ is chosen from the series consisting of hydrogen and    (C₁-C₈)-alkyl which is optionally substituted by one substituent    chosen from the series consisting (C₁-C₆)-alkyl-O— and    (C₁-C₆)-alkyl-C(O)—O—;-   R⁷² and R⁷³ are independently of each other chosen from the series    consisting of hydrogen and (C₁-C₂)-alkyl;-   Ar is chosen from the series consisting of phenyl and an aromatic    6-membered heterocycle which comprises one or two nitrogen atoms as    ring heteroatoms, wherein the phenyl and the heterocycle are all    optionally substituted by one, two or three identical or different    substituents chosen from the series consisting of halogen,    (C₁-C₆)-alkyl, (C₁-C₆)-alkyl-O—, (C₁-C₆)-alkyl-S(O)_(m)— and NC—;-   Het¹, independently of each other group Het¹, is a saturated or    unsaturated 4-membered to 6-membered monocyclic heterocycle which    comprises a ring nitrogen atom via which Het¹ is bonded and    optionally one further ring heteroatom chosen from the series    consisting of nitrogen, oxygen and sulfur, which is optionally    substituted by one, two or three identical or different substituents    chosen from the series consisting of fluorine, (C₁-C₄)-alkyl, HO—    and oxo;-   m, independently of each other number m, is an integer chosen from    the series consisting of 0, 1 and 2;-   wherein all cycloalkyl groups, independently of each other, are    optionally substituted by one or more identical or different    substituents chosen from the series consisting of fluorine and    (C₁-C₄)-alkyl;-   wherein all alkyl, C_(s)H_(2s) and C_(u)H_(2u) groups, independently    of each other, and independently of any other substituents, are    optionally substituted by one or more fluorine substituents;-   in any of their stereoisomeric forms or a mixture of stereoisomeric    forms in any ratio, and their physiologically acceptable salts, and    the physiologically acceptable solvates of any of them.

A subject of the invention also is a compound of the formula I which ischosen from any of the specific compounds of the formula I which aredisclosed herein, or is any one of the specific compounds of the formulaI which are disclosed herein, irrespective thereof whether they aredisclosed as a free compound and/or as a specific salt, or aphysiologically acceptable salt thereof, or a physiologically acceptablesolvate of any of them, wherein the compound of the formula I is asubject of the invention in any of its stereoisomeric forms or a mixtureof stereoisomeric forms in any ratio. For example, a subject of theinvention is a compound of the formula I which is chosen from

-   3-[(5-Hydroxy-1-phenyl-1H-pyrazole-3-carbonyl)-amino]-3-(4-methoxy-phenyl)-propionic    acid,-   3-(3-tert-Butoxy-phenyl)-3-{[1-(2,5-dimethyl-phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]-amino}-propionic    acid,-   (S)-3-{[1-(2-Fluoro-phenyl)-5-methoxy-1H-pyrazole-3-carbonyl]-amino}-3-o-tolyl-propionic    acid,-   3-(3-Fluoro-2-methyl-phenyl)-3-{[1-(4-fluoro-phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]-amino}-propionic    acid,-   3-(2-Chloro-5-fluoro-phenyl)-3-{[1-(4-fluoro-phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]-amino}-propionic    acid,-   (S)-3-[(5-Methoxy-1-phenyl-1H-pyrazole-3-carbonyl)-amino]-3-o-tolyl-propionic    acid,-   3-[(5-Hydroxy-1-phenyl-1H-pyrazole-3-carbonyl)-amino]-3-(2-methoxy-5-trifluoromethyl-phenyl)-propionic    acid,-   3-(2-Fluoro-4-methyl-phenyl)-3-[(5-hydroxy-1-phenyl-1H-pyrazole-3-carbonyl)-amino]-propionic    acid,-   3-{[1-(2-Chloro-phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]-amino}-3-(2′-fluoro-biphenyl-4-yl)-propionic    acid,-   3-[(5-Methoxy-1-phenyl-1H-pyrazole-3-carbonyl)-amino]-3-(4-pyridin-2-yl-phenyl)-propionic    acid,-   3-{[1-(2-Fluoro-phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]-amino}-3-(4-methanesulfonyl-phenyl)-propionic    acid,-   (S)-3-{[5-Hydroxy-1-(2-methanesulfonyl-phenyl)-1H)-pyrazole-3-carbonyl]-amino}-3-O—    tolyl-propionic acid,-   3-{[1-(2-Fluoro-phenyl)-5-methoxy-1H-pyrazole-3-carbonyl]-amino}-3-(4-methoxy-2-methyl-phenyl)-propionic    acid,-   (S)-3-{[1-(2-Fluoro-phenyl)-5-methoxy-1H-pyrazole-3-carbonyl]-amino}-3-(2-trifluoromethyl-phenyl)-propionic    acid,-   3-(2,3-Dimethyl-phenyl)-3-{[1-(2-fluoro-phenyl)-5-methoxy-1H-pyrazole-3-carbonyl]-amino}-propionic    acid,-   3-{[5-Cyclopropyl    methoxy-1-(2-fluoro-phenyl)-1H-pyrazole-3-carbonyl]-amino}-3-(3-fluoro-2-methyl-phenyl)-propionic    acid,-   (S)-3-{[5-Cyclopropyl    methoxy-1-(2-fluoro-phenyl)-1H-pyrazole-3-carbonyl]-amino}-3-m-tolyl-propionic    acid,-   (S)-3-{[1-(2-Fluoro-phenyl)-5-((R)-2-hydroxy-3,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-3-o-tolyl-propionic    acid,-   (S)-3-{[1-(2-Fluoro-phenyl)-5-((S)-2-hydroxy-3,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-3-o-tolyl-propionic    acid,-   (S)-3-{[5-(3,3-Dimethyl-2-oxo-butoxy)-1-(2-fluoro-phenyl)-1H-pyrazole-3-carbonyl]-amino}-3-o-tolyl-propionic    acid,-   (S)-3-(2,4-Dichloro-phenyl)-3-{[1-(2-fluoro-phenyl)-5-(2-hydroxy-2-methyl-propoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic    acid,-   (S)-3-{[5-(2-Cyclopropyl-2-hydroxy-propoxy)-1-(2-fluoro-phenyl)-1H-pyrazole-3-carbonyl]-amino}-3-o-tolyl-propionic    acid,-   (S)-3-{[1-(2-Fluoro-phenyl)-5-((R)-2-hydroxy-2,3,3-trimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-3-o-tolyl-propionic    acid,-   (S)-3-{[1-(2-Fluoro-phenyl)-5-((S)-2-hydroxy-2,3,3-trimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-3-o-tolyl-propionic    acid,-   (S)-3-(2-Chloro-phenyl)-3-{[1-(2-fluoro-phenyl)-5-((R)-2-hydroxy-2,3,3-trimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic    acid,-   (S)-3-(2-Chloro-phenyl)-3-{[1-(2-fluoro-phenyl)-5-((S)-2-hydroxy-2,3,3-trimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic    acid,-   (S)-3-(2,4-Dichloro-phenyl)-3-{[5-(2-ethyl-2-hydroxy-butoxy)-1-(2-fluoro-phenyl)-1H-pyrazole-3-carbonyl]-amino}-propionic    acid,-   (S)-3-(2,3-Dimethyl-phenyl)-3-{[1-(2-fluoro-phenyl)-5-((R)-2-hydroxy-3,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic    acid,-   (S)-3-(2,4-Dimethyl-phenyl)-3-{[1-(2-fluoro-phenyl)-5-((R)-2-hydroxy-3,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic    acid,-   (S)-3-(2,5-Dimethyl-phenyl)-3-{[1-(2-fluoro-phenyl)-5-((R)-2-hydroxy-3,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic    acid,-   (S)-3-(2-Chloro-phenyl)-3-{[1-(2-fluoro-phenyl)-5-((R)-2-hydroxy-3,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic    acid,-   (S)-3-(2,3-Dichloro-phenyl)-3-{[1-(2-fluoro-phenyl)-5-((R)-2-hydroxy-3,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic    acid,-   (S)-3-(2,4-Dichloro-phenyl)-3-{[1-(2-fluoro-phenyl)-5-((R)-2-hydroxy-3,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic    acid,-   (S)-3-(2,5-Dichloro-phenyl)-3-{[1-(2-fluoro-phenyl)-5-((R)-2-hydroxy-3,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic    acid,-   (S)-3-{[1-(2-Fluoro-phenyl)-5-((R)-2-hydroxy-3,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-3-(4-methoxy-2-methyl-phenyl)-propionic    acid,-   (S)-3-{[1-(2-Fluoro-phenyl)-5-((R)-2-hydroxy-3,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-3-(4-methoxy-phenyl)-propionic    acid,-   (S)-3-{[1-(2-Fluoro-phenyl)-5-((R)-2-hydroxy-3,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-3-(4-methanesulfonyl-phenyl)-propionic    acid,-   (S)-3-(2-Fluoro-phenyl)-3-{[1-(2-fluoro-phenyl)-5-((R)-2-hydroxy-3,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic    acid,-   (S)-3-{[1-(2-Fluoro-phenyl)-5-((R)-2-hydroxy-3,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-3-phenyl-propionic    acid,-   (S)-3-{[1-(2-Fluoro-phenyl)-5-((R)-2-hydroxy-3,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-3-(2-trifluoromethyl-phenyl)-propionic    acid,-   (S)-3-{[1-(2-Fluoro-phenyl)-5-((R)-2-hydroxy-3,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-3-(4-trifluoromethyl-phenyl)-propionic    acid,-   (S)-3-{[5-((R)-2-Hydroxy-3,3-dimethyl-butoxy)-1-phenyl-1H-pyrazole-3-carbonyl]-amino}-3-o-tolyl-propionic    acid,-   (S)-3-{[5-((R)-2-Hydroxy-3,3-dimethyl-butoxy)-1-phenyl-1H-pyrazole-3-carbonyl]-amino}-3-p-tolyl-propionic    acid,-   (S)-3-(2,3-Dimethyl-phenyl)-3-{[5-((R)-2-hydroxy-3,3-dimethyl-butoxy)-1-phenyl-1H-pyrazole-3-carbonyl]-amino}-propionic    acid,-   (S)-3-{[5-((R)-2-Hydroxy-3,3-dimethyl-butoxy)-1-phenyl-1H-pyrazole-3-carbonyl]-amino}-3-phenyl-propionic    acid,-   (S)-3-(2-Chloro-phenyl)-3-{[5-((R)-2-hydroxy-3,3-dimethyl-butoxy)-1-phenyl-1H-pyrazole-3-carbonyl]-amino}-propionic    acid,-   (S)-3-(2,3-Dichloro-phenyl)-3-{[5-((R)-2-hydroxy-3,3-dimethyl-butoxy)-1-phenyl-1H-pyrazole-3-carbonyl]-amino}-propionic    acid,-   (S)-3-(2,4-Dichloro-phenyl)-3-{[5-((R)-2-hydroxy-3,3-dimethyl-butoxy)-1-phenyl-1H-pyrazole-3-carbonyl]-amino}-propionic    acid,-   (S)-3-(2,4-Dichloro-phenyl)-3-{[1-(3-fluoro-phenyl)-5-((R)-2-hydroxy-3,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic    acid,-   (S)-3-{[1-(3-Fluoro-phenyl)-5-((R)-2-hydroxy-3,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-3-o-tolyl-propionic    acid,-   (S)-3-(2,4-Dimethyl-phenyl)-3-{[1-(3-fluoro-phenyl)-5-((R)-2-hydroxy-3,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic    acid,-   (S)-3-{[1-(2-Chloro-phenyl)-5-((R)-2-hydroxy-3,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-3-o-tolyl-propionic    acid,-   (S)-3-{[1-(2-Chloro-phenyl)-5-((R)-2-hydroxy-3,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-3-m-tolyl-propionic    acid,-   (S)-3-{[1-(2-Chloro-phenyl)-5-((R)-2-hydroxy-3,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-3-m-tolyl-propionic    acid,-   (S)-3-(2-Chloro-phenyl)-3-{[1-(2-chloro-phenyl)-5-((R)-2-hydroxy-3,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic    acid,-   (S)-3-{[1-(2-Chloro-phenyl)-5-((R)-2-hydroxy-3,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-3-(2,3-dichloro-phenyl)-propionic    acid,-   (S)-3-{[1-(2-Chloro-phenyl)-5-((R)-2-hydroxy-3,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-3-(2,4-dichloro-phenyl)-propionic    acid,-   (S)-3-{[1-(2-Chloro-phenyl)-5-((R)-2-hydroxy-3,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-3-phenyl-propionic    acid,-   (S)-3-{[1-(4-Fluoro-phenyl)-5-((R)-2-hydroxy-3,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-3-phenyl-propionic    acid,-   (S)-3-{[1-(4-Fluoro-phenyl)-5-((R)-2-hydroxy-3,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-3-o-tolyl-propionic    acid,-   (S)-3-(2,3-Dimethyl-phenyl)-3-{[1-(2-fluoro-phenyl)-5-((S)-2-hydroxy-3,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic    acid,-   (S)-3-(2,4-Dimethyl-phenyl)-3-{[1-(2-fluoro-phenyl)-5-((S)-2-hydroxy-3,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic    acid,-   (S)-3-(2,5-Dimethyl-phenyl)-3-{[1-(2-fluoro-phenyl)-5-((S)-2-hydroxy-3,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic    acid,-   (S)-3-(2-Chloro-phenyl)-3-{[1-(2-fluoro-phenyl)-5-((S)-2-hydroxy-3,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic    acid,-   (S)-3-(2,3-Dichloro-phenyl)-3-{[1-(2-fluoro-phenyl)-5-((S)-2-hydroxy-3,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic    acid,-   (S)-3-(2,4-Dichloro-phenyl)-3-{[1-(2-fluoro-phenyl)-5-((S)-2-hydroxy-3,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic    acid,-   (S)-3-(2,5-Dichloro-phenyl)-3-{[1-(2-fluoro-phenyl)-5-((S)-2-hydroxy-3,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic    acid,-   (S)-3-{[1-(2-Fluoro-phenyl)-5-((S)-2-hydroxy-3,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-3-(4-methoxy-2-methyl-phenyl)-propionic    acid,-   (S)-3-{[1-(2-Fluoro-phenyl)-5-((S)-2-hydroxy-3,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-3-(4-methoxy-phenyl)-propionic    acid,-   (S)-3-{[1-(2-Fluoro-phenyl)-5-((S)-2-hydroxy-3,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-3-(4-methanesulfonyl-phenyl)-propionic    acid,-   (S)-3-(2-Fluoro-phenyl)-3-{[1-(2-fluoro-phenyl)-5-((S)-2-hydroxy-3,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic    acid,-   (S)-3-{[1-(2-Fluoro-phenyl)-5-((S)-2-hydroxy-3,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-3-phenyl-propionic    acid,-   (S)-3-{[1-(2-Fluoro-phenyl)-5-((S)-2-hydroxy-3,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-3-(2-trifluoromethyl-phenyl)-propionic    acid,-   (S)-3-{[1-(2-Fluoro-phenyl)-5-((S)-2-hydroxy-3,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-3-(4-trifluoromethyl-phenyl)-propionic    acid,-   (S)-3-{[5-((S)-2-Hydroxy-3,3-dimethyl-butoxy)-1-phenyl-1H-pyrazole-3-carbonyl]-amino}-3-o-tolyl-propionic    acid,-   (S)-3-{[5-((S)-2-Hydroxy-3,3-dimethyl-butoxy)-1-phenyl-1H-pyrazole-3-carbonyl]-amino}-3-p-tolyl-propionic    acid,-   (S)-3-(2,3-Dimethyl-phenyl)-3-{[5-((S)-2-hydroxy-3,3-dimethyl-butoxy)-1-phenyl-1H-pyrazole-3-carbonyl]-amino}-propionic    acid,-   (S)-3-{[5-((S)-2-Hydroxy-3,3-dimethyl-butoxy)-1-phenyl-1H-pyrazole-3-carbonyl]-amino}-3-phenyl-propionic    acid,-   (S)-3-(2-Chloro-phenyl)-3-{[5-((S)-2-hydroxy-3,3-dimethyl-butoxy)-1-phenyl-1H-pyrazole-3-carbonyl]-amino}-propionic    acid,-   (S)-3-(2,3-Dichloro-phenyl)-3-{[5-((S)-2-hydroxy-3,3-dimethyl-butoxy)-1-phenyl-1H-pyrazole-3-carbonyl]-amino}-propionic    acid,-   (S)-3-(2,4-Dichloro-phenyl)-3-{[5-((S)-2-hydroxy-3,3-dimethyl-butoxy)-1-phenyl-1H-pyrazole-3-carbonyl]-amino}-propionic    acid,-   (S)-3-(2,4-Dichloro-phenyl)-3-{[1-(3-fluoro-phenyl)-5-((S)-2-hydroxy-3,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic    acid,-   (S)-3-{[1-(3-Fluoro-phenyl)-5-((S)-2-hydroxy-3,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-3-o-tolyl-propionic    acid,-   (S)-3-(2,4-Dimethyl-phenyl)-3-{[1-(3-fluoro-phenyl)-5-((S)-2-hydroxy-3,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic    acid,-   (S)-3-{[1-(2-Chloro-phenyl)-5-((S)-2-hydroxy-3,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-3-o-tolyl-propionic    acid,-   (S)-3-{[1-(2-Chloro-phenyl)-5-((S)-2-hydroxy-3,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-3-m-tolyl-propionic    acid,-   (S)-3-{[1-(2-Chloro-phenyl)-5-((S)-2-hydroxy-3,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-3-m-tolyl-propionic    acid,-   (S)-3-(2-Chloro-phenyl)-3-{[1-(2-chloro-phenyl)-5-((S)-2-hydroxy-3,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic    acid,-   (S)-3-{[1-(2-Chloro-phenyl)-5-((S)-2-hydroxy-3,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-3-(2,3-dichloro-phenyl)-propionic    acid,-   (S)-3-{[1-(2-Chloro-phenyl)-5-((S)-2-hydroxy-3,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-3-(2,4-dichloro-phenyl)-propionic    acid,-   (S)-3-{[1-(2-Chloro-phenyl)-5-((S)-2-hydroxy-3,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-3-phenyl-propionic    acid,-   (S)-3-{[1-(4-Fluoro-phenyl)-5-((S)-2-hydroxy-3,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-3-phenyl-propionic    acid,-   (S)-3-{[1-(4-Fluoro-phenyl)-5-((S)-2-hydroxy-3,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-3-o-tolyl-propionic    acid,-   (S)-3-{[1-(2-Fluoro-phenyl)-5-((R)-2-hydroxy-2,3,3-trimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-3-m-tolyl-propionic    acid,-   (S)-3-{[1-(3-Fluoro-phenyl)-5-((R)-2-hydroxy-2,3,3-trimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-3-o-tolyl-propionic    acid,-   (S)-3-{[1-(4-Fluoro-phenyl)-5-((R)-2-hydroxy-2,3,3-trimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-3-o-tolyl-propionic    acid,-   (S)-3-{[1-(2-Chloro-phenyl)-5-((R)-2-hydroxy-2,3,3-trimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-3-o-tolyl-propionic    acid,-   (S)-3-{[5-((R)-2-Hydroxy-2,3,3-trimethyl-butoxy)-1-phenyl-1H-pyrazole-3-carbonyl]-amino}-3-o-tolyl-propionic    acid,-   (S)-3-{[1-(2-Chloro-phenyl)-5-((R)-2-hydroxy-2,3,3-trimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-3-m-tolyl-propionic    acid,-   (S)-3-{[1-(3-Fluoro-phenyl)-5-((R)-2-hydroxy-2,3,3-trimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-3-m-tolyl-propionic    acid,-   (S)-3-{[5-((R)-2-Hydroxy-2,3,3-trimethyl-butoxy)-1-phenyl-1H-pyrazole-3-carbonyl]-amino}-3-m-tolyl-propionic    acid,-   (S)-3-{[1-(2-Fluoro-phenyl)-5-((R)-2-hydroxy-2,3,3-trimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-3-p-tolyl-propionic    acid,-   (S)-3-{[1-(3-Fluoro-phenyl)-5-((R)-2-hydroxy-2,3,3-trimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-3-p-tolyl-propionic    acid,-   (S)-3-{[1-(4-Fluoro-phenyl)-5-((R)-2-hydroxy-2,3,3-trimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-3-p-tolyl-propionic    acid,-   (S)-3-{[1-(2-Chloro-phenyl)-5-((R)-2-hydroxy-2,3,3-trimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-3-p-tolyl-propionic    acid,-   (S)-3-(2,3-Dimethyl-phenyl)-3-{[5-((R)-2-hydroxy-2,3,3-trimethyl-butoxy)-1-phenyl-1H-pyrazole-3-carbonyl]-amino}-propionic    acid,-   (S)-3-(2,3-Dimethyl-phenyl)-3-{[1-(2-fluoro-phenyl)-5-((R)-2-hydroxy-2,3,3-trimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic    acid,-   (S)-3-(2,3-Dimethyl-phenyl)-3-{[1-(3-fluoro-phenyl)-5-((R)-2-hydroxy-2,3,3-trimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic    acid,-   (S)-3-(2,3-Dimethyl-phenyl)-3-{[1-(4-fluoro-phenyl)-5-((R)-2-hydroxy-2,3,3-trimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic    acid,-   (S)-3-(2,4-Dimethyl-phenyl)-3-{[5-((R)-2-hydroxy-2,3,3-trimethyl-butoxy)-1-phenyl-1H-pyrazole-3-carbonyl]-amino}-propionic    acid,-   (S)-3-(2,4-Dimethyl-phenyl)-3-{[1-(2-fluoro-phenyl)-5-((R)-2-hydroxy-2,3,3-trimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic    acid,-   (S)-3-(2,4-Dimethyl-phenyl)-3-{[1-(3-fluoro-phenyl)-5-((R)-2-hydroxy-2,3,3-trimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic    acid,-   (S)-3-(2,4-Dimethyl-phenyl)-3-{[1-(4-fluoro-phenyl)-5-((R)-2-hydroxy-2,3,3-trimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic    acid,-   (S)-3-{[1-(2-Chloro-phenyl)-5-((R)-2-hydroxy-2,3,3-trimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-3-(2,4-dimethyl-phenyl)-propionic    acid,-   (S)-3-(2-Chloro-phenyl)-3-{[5-((R)-2-hydroxy-2,3,3-trimethyl-butoxy)-1-phenyl-1H-pyrazole-3-carbonyl]-amino}-propionic    acid,-   (S)-3-(2-Chloro-phenyl)-3-{[1-(2-chloro-phenyl)-5-((R)-2-hydroxy-2,3,3-trimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic    acid,-   (S)-3-(2-Chloro-phenyl)-3-{[1-(3-fluoro-phenyl)-5-((R)-2-hydroxy-2,3,3-trimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic    acid,-   (S)-3-(2-Chloro-phenyl)-3-{[1-(4-fluoro-phenyl)-5-((R)-2-hydroxy-2,3,3-trimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic    acid,-   (S)-3-(2,3-Dichloro-phenyl)-3-{[5-((R)-2-hydroxy-2,3,3-trimethyl-butoxy)-1-phenyl-1H-pyrazole-3-carbonyl]-amino}-propionic    acid,-   (S)-3-(2,3-Dichloro-phenyl)-3-{[1-(2-fluoro-phenyl)-5-((R)-2-hydroxy-2,3,3-trimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic    acid,-   (S)-3-(2,3-Dichloro-phenyl)-3-{[1-(3-fluoro-phenyl)-5-((R)-2-hydroxy-2,3,3-trimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic    acid,-   (S)-3-(2,3-Dichloro-phenyl)-3-{[1-(4-fluoro-phenyl)-5-((R)-2-hydroxy-2,3,3-trimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic    acid,-   (S)-3-(2,4-Dichloro-phenyl)-3-{[5-((R)-2-hydroxy-2,3,3-trimethyl-butoxy)-1-phenyl-1H-pyrazole-3-carbonyl]-amino}-propionic    acid,-   (S)-3-(2,4-Dichloro-phenyl)-3-{[1-(2-fluoro-phenyl)-5-((R)-2-hydroxy-2,3,3-trimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic    acid,-   (S)-3-(2,4-Dichloro-phenyl)-3-{[1-(3-fluoro-phenyl)-5-((R)-2-hydroxy-2,3,3-trimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic    acid,-   (S)-3-(2,4-Dichloro-phenyl)-3-{[1-(4-fluoro-phenyl)-5-((R)-2-hydroxy-2,3,3-trimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic    acid,-   (S)-3-(2,5-Dichloro-phenyl)-3-{[5-((R)-2-hydroxy-2,3,3-trimethyl-butoxy)-1-phenyl-1H-pyrazole-3-carbonyl]-amino}-propionic    acid,-   (S)-3-(2,5-Dichloro-phenyl)-3-{[1-(2-fluoro-phenyl)-5-((R)-2-hydroxy-2,3,3-trimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic    acid,-   (S)-3-{[1-(2-Fluoro-phenyl)-5-((S)-2-hydroxy-2,3,3-trimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-3-m-tolyl-propionic    acid,-   (S)-3-{[1-(3-Fluoro-phenyl)-5-((S)-2-hydroxy-2,3,3-trimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-3-o-tolyl-propionic    acid,-   (S)-3-{[1-(4-Fluoro-phenyl)-5-((S)-2-hydroxy-2,3,3-trimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-3-o-tolyl-propionic    acid,-   (S)-3-{[1-(2-Chloro-phenyl)-5-((S)-2-hydroxy-2,3,3-trimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-3-o-tolyl-propionic    acid,-   (S)-3-{[5-((S)-2-Hydroxy-2,3,3-trimethyl-butoxy)-1-phenyl-1H-pyrazole-3-carbonyl]-amino}-3-o-tolyl-propionic    acid,-   (S)-3-{[1-(2-Chloro-phenyl)-5-((S)-2-hydroxy-2,3,3-trimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-3-m-tolyl-propionic    acid,-   (S)-3-{[1-(3-Fluoro-phenyl)-5-((S)-2-hydroxy-2,3,3-trimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-3-m-tolyl-propionic    acid,-   (S)-3-{[5-((S)-2-Hydroxy-2,3,3-trimethyl-butoxy)-1-phenyl-1H-pyrazole-3-carbonyl]-amino}-3-m-tolyl-propionic    acid,-   (S)-3-{[1-(2-Fluoro-phenyl)-5-((S)-2-hydroxy-2,3,3-trimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-3-p-tolyl-propionic    acid,-   (S)-3-{[1-(3-Fluoro-phenyl)-5-((S)-2-hydroxy-2,3,3-trimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-3-p-tolyl-propionic    acid,-   (S)-3-{[1-(4-Fluoro-phenyl)-5-((S)-2-hydroxy-2,3,3-trimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-3-p-tolyl-propionic    acid,-   (S)-3-{[1-(2-Chloro-phenyl)-5-((S)-2-hydroxy-2,3,3-trimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-3-p-tolyl-propionic    acid,-   (S)-3-(2,3-Dimethyl-phenyl)-3-{[5-((S)-2-hydroxy-2,3,3-trimethyl-butoxy)-1-phenyl-1H-pyrazole-3-carbonyl]-amino}-propionic    acid,-   (S)-3-(2,3-Dimethyl-phenyl)-3-{[1-(2-fluoro-phenyl)-5-((S)-2-hydroxy-2,3,3-trimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic    acid,-   (S)-3-(2,3-Dimethyl-phenyl)-3-{[1-(3-fluoro-phenyl)-5-((S)-2-hydroxy-2,3,3-trimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic    acid,-   (S)-3-(2,3-Dimethyl-phenyl)-3-{[1-(4-fluoro-phenyl)-5-((S)-2-hydroxy-2,3,3-trimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic    acid,-   (S)-3-(2,4-Dimethyl-phenyl)-3-{[5-((S)-2-hydroxy-2,3,3-trimethyl-butoxy)-1-phenyl-1H-pyrazole-3-carbonyl]-amino}-propionic    acid,-   (S)-3-(2,4-Dimethyl-phenyl)-3-{[1-(2-fluoro-phenyl)-5-((S)-2-hydroxy-2,3,3-trimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic    acid,-   (S)-3-(2,4-Dimethyl-phenyl)-3-{[1-(3-fluoro-phenyl)-5-((S)-2-hydroxy-2,3,3-trimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic    acid,-   (S)-3-(2,4-Dimethyl-phenyl)-3-{[1-(4-fluoro-phenyl)-5-((S)-2-hydroxy-2,3,3-trimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic    acid,-   (S)-3-{[1-(2-Chloro-phenyl)-5-((S)-2-hydroxy-2,3,3-trimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-3-(2,4-dimethyl-phenyl)-propionic    acid,-   (S)-3-(2-Chloro-phenyl)-3-{[5-((S)-2-hydroxy-2,3,3-trimethyl-butoxy)-1-phenyl-1H-pyrazole-3-carbonyl]-amino}-propionic    acid,-   (S)-3-(2-Chloro-phenyl)-3-{[1-(2-chloro-phenyl)-5-((S)-2-hydroxy-2,3,3-trimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic    acid,-   (S)-3-(2-Chloro-phenyl)-3-{[1-(3-fluoro-phenyl)-5-((S)-2-hydroxy-2,3,3-trimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic    acid,-   (S)-3-(2-Chloro-phenyl)-3-{[1-(4-fluoro-phenyl)-5-((S)-2-hydroxy-2,3,3-trimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic    acid,-   (S)-3-(2,3-Dichloro-phenyl)-3-{[5-((S)-2-hydroxy-2,3,3-trimethyl-butoxy)-1-phenyl-1H-pyrazole-3-carbonyl]-amino}-propionic    acid,-   (S)-3-(2,3-Dichloro-phenyl)-3-{[1-(2-fluoro-phenyl)-5-((S)-2-hydroxy-2,3,3-trimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic    acid,-   (S)-3-(2,3-Dichloro-phenyl)-3-{[1-(3-fluoro-phenyl)-5-((S)-2-hydroxy-2,3,3-trimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic    acid,-   (S)-3-(2,3-Dichloro-phenyl)-3-{[1-(4-fluoro-phenyl)-5-((S)-2-hydroxy-2,3,3-trimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic    acid,-   (S)-3-(2,4-Dichloro-phenyl)-3-{[5-((S)-2-hydroxy-2,3,3-trimethyl-butoxy)-1-phenyl-1H-pyrazole-3-carbonyl]-amino}-propionic    acid,-   (S)-3-(2,4-Dichloro-phenyl)-3-{[1-(2-fluoro-phenyl)-5-((S)-2-hydroxy-2,3,3-trimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic    acid,-   (S)-3-(2,4-Dichloro-phenyl)-3-{[1-(3-fluoro-phenyl)-5-((S)-2-hydroxy-2,3,3-trimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic    acid,-   (S)-3-(2,4-Dichloro-phenyl)-3-{[1-(4-fluoro-phenyl)-5-((S)-2-hydroxy-2,3,3-trimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic    acid,-   (S)-3-(2,5-Dichloro-phenyl)-3-{[5-((S)-2-hydroxy-2,3,3-trimethyl-butoxy)-1-phenyl-1H-pyrazole-3-carbonyl]-amino}-propionic    acid,-   (S)-3-(2,5-Dichloro-phenyl)-3-{[1-(2-fluoro-phenyl)-5-((S)-2-hydroxy-2,3,3-trimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic    acid,-   (S)-3-{[1-(2-Fluoro-phenyl)-5-((R)-2-hydroxy-2,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-3-o-tolyl-propionic    acid,-   (S)-3-{[5-((R)-2-Hydroxy-2,3-dimethyl-butoxy)-1-phenyl-1H-pyrazole-3-carbonyl]-amino}-3-o-tolyl-propionic    acid,-   (S)-3-{[1-(3-Fluoro-phenyl)-5-((R)-2-hydroxy-2,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-3-o-tolyl-propionic    acid,-   (S)-3-{[1-(4-Fluoro-phenyl)-5-((R)-2-hydroxy-2,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-3-o-tolyl-propionic    acid,-   (S)-3-{[1-(2-Chloro-phenyl)-5-((R)-2-hydroxy-2,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-3-o-tolyl-propionic    acid,-   (S)-3-{[5-((R)-2-Hydroxy-2,3-dimethyl-butoxy)-1-phenyl-1H-pyrazole-3-carbonyl]-amino}-3-phenyl-propionic    acid,-   (S)-3-(2-Chloro-phenyl)-3-{[1-(2-fluoro-phenyl)-5-((R)-2-hydroxy-2,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic    acid,-   (S)-3-(2-Chloro-phenyl)-3-{[1-(3-fluoro-phenyl)-5-((R)-2-hydroxy-2,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic    acid,-   (S)-3-(2,3-Dichloro-phenyl)-3-{[5-((R)-2-hydroxy-2,3-dimethyl-butoxy)-1-phenyl-1H-pyrazole-3-carbonyl]-amino}-propionic    acid,-   (S)-3-(2,3-Dichloro-phenyl)-3-{[1-(2-fluoro-phenyl)-5-((R)-2-hydroxy-2,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic    acid,-   S)-3-(2,3-Dichloro-phenyl)-3-{[1-(3-fluoro-phenyl)-5-((R)-2-hydroxy-2,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic    acid,-   (S)-3-(2,4-Dichloro-phenyl)-3-{[5-((R)-2-hydroxy-2,3-dimethyl-butoxy)-1-phenyl-1H-pyrazole-3-carbonyl]-amino}-propionic    acid,-   (S)-3-(2,4-Dichloro-phenyl)-3-{[1-(2-fluoro-phenyl)-5-((R)-2-hydroxy-2,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic    acid,-   (S)-3-{[1-(2-Fluoro-phenyl)-5-((R)-2-hydroxy-2,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-3-p-tolyl-propionic    acid,-   (S)-3-{[5-((R)-2-Hydroxy-2,3-dimethyl-butoxy)-1-phenyl-1H-pyrazole-3-carbonyl]-amino}-3-p-tolyl-propionic    acid,-   S)-3-(2,4-Dimethyl-phenyl)-3-{[5-((R)-2-hydroxy-2,3-dimethyl-butoxy)-1-phenyl-1H-pyrazole-3-carbonyl]-amino}-propionic    acid,-   (S)-3-(2,4-Dimethyl-phenyl)-3-{[1-(2-fluoro-phenyl)-5-((R)-2-hydroxy-2,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic    acid,-   (S)-3-{[1-(2-Fluoro-phenyl)-5-((S)-2-hydroxy-2,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-3-o-tolyl-propionic    acid,-   (S)-3-{[5-((S)-2-Hydroxy-2,3-dimethyl-butoxy)-1-phenyl-1H-pyrazole-3-carbonyl]-amino}-3-o-tolyl-propionic    acid,-   (S)-3-{[1-(3-Fluoro-phenyl)-5-((S)-2-hydroxy-2,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-3-o-tolyl-propionic    acid,-   (S)-3-{[1-(4-Fluoro-phenyl)-5-((S)-2-hydroxy-2,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-3-o-tolyl-propionic    acid,-   (S)-3-{[1-(2-Chloro-phenyl)-5-((S)-2-hydroxy-2,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-3-o-tolyl-propionic    acid,-   (S)-3-{[5-((S)-2-Hydroxy-2,3-dimethyl-butoxy)-1-phenyl-1H-pyrazole-3-carbonyl]-amino}-3-phenyl-propionic    acid,-   (S)-3-(2-Chloro-phenyl)-3-{[1-(2-fluoro-phenyl)-5-((S)-2-hydroxy-2,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic    acid,-   (S)-3-(2-Chloro-phenyl)-3-{[1-(3-fluoro-phenyl)-5-((S)-2-hydroxy-2,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic    acid,-   (S)-3-(2,3-Dichloro-phenyl)-3-{[5-((S)-2-hydroxy-2,3-dimethyl-butoxy)-1-phenyl-1H-pyrazole-3-carbonyl]-amino}-propionic    acid,-   (S)-3-(2,3-Dichloro-phenyl)-3-{[1-(2-fluoro-phenyl)-5-((S)-2-hydroxy-2,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic    acid,-   S)-3-(2,3-Dichloro-phenyl)-3-{[1-(3-fluoro-phenyl)-5-((S)-2-hydroxy-2,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic    acid,-   (S)-3-(2,4-Dichloro-phenyl)-3-{[5-((S)-2-hydroxy-2,3-dimethyl-butoxy)-1-phenyl-1H-pyrazole-3-carbonyl]-amino}-propionic    acid,-   (S)-3-(2,4-Dichloro-phenyl)-3-{[1-(2-fluoro-phenyl)-5-((S)-2-hydroxy-2,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic    acid,-   (S)-3-{[1-(2-Fluoro-phenyl)-5-((S)-2-hydroxy-2,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-3-p-tolyl-propionic    acid,-   (S)-3-{[5-((S)-2-Hydroxy-2,3-dimethyl-butoxy)-1-phenyl-1H-pyrazole-3-carbonyl]-amino}-3-p-tolyl-propionic    acid,-   S)-3-(2,4-Dimethyl-phenyl)-3-{[5-((S)-2-hydroxy-2,3-dimethyl-butoxy)-1-phenyl-1H-pyrazole-3-carbonyl]-amino}-propionic    acid,-   (S)-3-(2,4-Dimethyl-phenyl)-3-{[1-(2-fluoro-phenyl)-5-((S)-2-hydroxy-2,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic    acid,-   (S)-3-{[1-(2-Fluoro-phenyl)-5-(2-hydroxy-2,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-3-o-tolyl-propionic    acid,-   (S)-3-(4-Fluoro-phenyl)-3-{[1-(2-fluoro-phenyl)-5-((R)-2-hydroxy-2,3,3-trimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic    acid,-   (S)-3-(2,4-Dimethyl-phenyl)-3-{[1-(2-fluoro-phenyl)-5-((S)-2-hydroxy-2,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic    acid,-   3-Cyclohexyl-3-{[1-(2-fluoro-phenyl)-5-((S)-2-hydroxy-2,3,3-trimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic    acid,-   (S)-3-(3-Chloro-phenyl)-3-{[1-(2-fluoro-phenyl)-5-((R)-2-hydroxy-2,3,3-trimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic    acid,-   (S)-3-(2-Chloro-phenyl)-3-{[1-(2-fluoro-phenyl)-5-(2-hydroxy-2,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic    acid,-   (S)-3-(2,3-Dichloro-phenyl)-3-{[1-(2-fluoro-phenyl)-5-((R)-2-hydroxy-3,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic    acid,-   (S)-3-(2-Chloro-phenyl)-3-{[5-(3,3-dimethyl-2-oxo-butoxy)-1-(2-fluoro-phenyl)-1H-pyrazole-3-carbonyl]-amino}-propionic    acid,-   (S)-3-(3-Cyano-phenyl)-3-{[1-(2-fluoro-phenyl)-5-((R)-2-hydroxy-2,3,3-trimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic    acid,-   (S)-3-(3-Fluoro-phenyl)-3-{[1-(2-fluoro-phenyl)-5-((R)-2-hydroxy-2,3,3-trimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic    acid,-   (S)-3-{[1-(2-Fluoro-phenyl)-5-((R)-2-hydroxy-2,3,3-trimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-3-p-tolyl-propionic    acid,-   (S)-3-{[1-(2-Fluoro-phenyl)-5-((S)-2-hydroxy-2,3,3-trimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-3-p-tolyl-propionic    acid,-   (S)-3-(3-Fluoro-phenyl)-3-{[1-(2-fluoro-phenyl)-5-(2-hydroxy-2,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic    acid,-   (S)-3-{[1-(2-Fluoro-phenyl)-5-((S)-2-hydroxy-2,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-3-(2-methoxy-phenyl)-propionic    acid,-   (S)-3-{[1-(2-Fluoro-phenyl)-5-((S)-2-hydroxy-2,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-3-(2-trifluoromethyl-phenyl)-propionic    acid,-   (S)-3-(3-Chloro-phenyl)-3-{[1-(2-fluoro-phenyl)-5-(2-hydroxy-2,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic    acid,-   3-Cyclohexyl-3-{[1-(2-fluoro-phenyl)-5-((R)-2-hydroxy-2,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic    acid,-   (S)-3-{[1-(2-Fluoro-phenyl)-5-(2-hydroxy-2,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-3-p-tolyl-propionic    acid-   (S)-3-{[1-(2-Fluoro-phenyl)-5-((R)-2-hydroxy-3,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-3-p-tolyl-propionic    acid,-   (S)-3-(2-Chloro-phenyl)-3-{[1-(2-fluoro-phenyl)-5-((S)-2-hydroxy-2,3,3-trimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic    acid,-   (S)-3-(2-Chloro-phenyl)-3-{[1-(2-fluoro-phenyl)-5-((R)-2-hydroxy-2,3,3-trimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic    acid,-   (S)-3-{[5-(3,3-Dimethyl-2-oxo-butoxy)-1-(2-fluoro-phenyl)-1H-pyrazole-3-carbonyl]-amino}-3-p-tolyl-propionic    acid,-   (S)-3-{[1-(2-Fluoro-phenyl)-5-((S)-2-hydroxy-3,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-3-m-tolyl-propionic    acid,-   (S)-3-(2-Chloro-phenyl)-3-{[1-(2-fluoro-phenyl)-5-((R)-2-hydroxy-3,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic    acid,-   (S)-3-(4-Chloro-phenyl)-3-{[1-(2-fluoro-phenyl)-5-((S)-2-hydroxy-3,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic    acid,-   (S)-3-(3-Chloro-phenyl)-3-{[1-(2-fluoro-phenyl)-5-((R)-2-hydroxy-3,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic    acid,-   (S)-3-(3-Chloro-phenyl)-3-{[5-(3,3-dimethyl-2-oxo-butoxy)-1-(2-fluoro-phenyl)-1H-pyrazole-3-carbonyl]-amino}-propionic    acid,-   (S)-3-(2-Chloro-phenyl)-3-{[1-(2-fluoro-phenyl)-5-((S)-2-hydroxy-3,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic    acid,-   (S)-3-(3-Chloro-phenyl)-3-{[1-(2-fluoro-phenyl)-5-((S)-2-hydroxy-2,3,3-trimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic    acid,-   (S)-3-{[1-(2-Fluoro-phenyl)-5-((S)-2-hydroxy-2,3,3-trimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-3-(2-trifluoromethyl-phenyl)-propionic    acid,-   (S)-3-(2,3-Dichloro-phenyl)-3-{[1-(2-fluoro-phenyl)-5-((S)-2-hydroxy-3,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic    acid,-   (S)-3-{[1-(2-Fluoro-phenyl)-5-((S)-2-hydroxy-3,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-3-p-tolyl-propionic    acid,-   (S)-3-{[1-(2-Fluoro-phenyl)-5-(2-hydroxy-2,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-3-(3-methoxy-phenyl)-propionic    acid,-   3-Cyclohexyl-3-{[1-(2-fluoro-phenyl)-5-((S)-2-hydroxy-2,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic    acid,-   (S)-3-{[1-(2-Fluoro-phenyl)-5-((R)-2-hydroxy-3,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-3-m-tolyl-propionic    acid,-   (S)-3-{[5-(3,3-Dimethyl-2-oxo-butoxy)-1-(2-fluoro-phenyl)-1H-pyrazole-3-carbonyl]-amino}-3-m-tolyl-propionic    acid,-   (S)-3-{[1-(2-Fluoro-phenyl)-5-((R)-2-hydroxy-2,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-3-(3-methoxy-phenyl)-propionic    acid,-   (S)-3-(3-Cyano-phenyl)-3-{[1-(2-fluoro-phenyl)-5-(2-hydroxy-2,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic    acid,-   (S)-3-(2,6-Difluoro-phenyl)-3-{[1-(2-fluoro-phenyl)-5-(2-hydroxy-2,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic    acid,-   (S)-3-(3-Chloro-phenyl)-3-{[1-(2-fluoro-phenyl)-5-((S)-2-hydroxy-3,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic    acid,-   (S)-3-{[1-(2-Fluoro-phenyl)-5-((S)-2-hydroxy-2,3,3-trimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-3-(2-methoxy-phenyl)-propionic    acid,-   (S)-3-{[1-(2-Fluoro-phenyl)-5-(2-hydroxy-2,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-3-(2-methoxy-phenyl)-propionic    acid,-   (S)-3-{[1-(2-Fluoro-phenyl)-5-(2-hydroxy-2,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-3-(2-trifluoromethyl-phenyl)-propionic    acid,-   3-Cyclohexyl-3-{[1-(2-fluoro-phenyl)-5-(2-hydroxy-2,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic    acid,-   3-{[1-(2-Fluoro-phenyl)-5-(2-hydroxy-2,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-5-methyl-hexanoic    acid,-   (R)-3-(4-Chloro-phenyl)-3-{[1-(2-fluoro-phenyl)-5-(2-hydroxy-3,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic    acid,-   (S)-3-(2,4-Dichloro-phenyl)-3-{[1-(2-fluoro-phenyl)-5-((R)-2-hydroxy-2,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic    acid,-   (S)-3-(2,6-Difluoro-phenyl)-3-{[1-(2-fluoro-phenyl)-5-((S)-2-hydroxy-2,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic    acid,-   3-{[1-(2-Fluoro-phenyl)-5-((S)-2-hydroxy-2,3,3-trimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-4-phenyl-butyric    acid,-   (S)-3-(3-Fluoro-phenyl)-3-{[1-(2-fluoro-phenyl)-5-((S)-2-hydroxy-2,3,3-trimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic    acid,-   3-Cyclohexyl-3-{[1-(2-fluoro-phenyl)-5-((R)-2-hydroxy-2,3,3-trimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic    acid,-   3-{[1-(2-Fluoro-phenyl)-5-((R)-2-hydroxy-2,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-4-phenyl-butyric    acid,-   (S)-3-{[1-(2-Fluoro-phenyl)-5-((R)-2-hydroxy-2,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-3-(2-methoxy-phenyl)-propionic    acid,-   3-{[1-(2-Fluoro-phenyl)-5-((R)-2-hydroxy-2,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-5-methyl-hexanoic    acid,-   (1-{[1-(2-Fluoro-phenyl)-5-((R)-2-hydroxy-2,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-cyclopentyl)-acetic    acid,-   (1-{[1-(2-Fluoro-phenyl)-5-((S)-2-hydroxy-2,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-cyclopentyl)-acetic    acid,-   3-{[1-(2-Fluoro-phenyl)-5-((S)-2-hydroxy-2,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-4-phenyl-butyric    acid,-   3-{[1-(2-Fluoro-phenyl)-5-((R)-2-hydroxy-2,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-2-phenyl-propionic    acid,-   (S)-3-(4-Chloro-phenyl)-3-{[1-(2-fluoro-phenyl)-5-((R)-2-hydroxy-3,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic    acid,-   3-{[1-(2-Fluoro-phenyl)-5-(2-hydroxy-2,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-4-phenyl-butyric    acid,-   3-{[1-(2-Fluoro-phenyl)-5-((S)-2-hydroxy-2,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-2-phenyl-propionic    acid,-   (S)-4-(4-Cyano-phenyl)-3-{[1-(2-fluoro-phenyl)-5-((S)-2-hydroxy-2,3,3-trimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-butyric    acid,-   (S)-3-{[1-(2-Fluoro-phenyl)-5-((S)-2-hydroxy-2,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-3-o-tolyl-propionic    acid,-   (S)-4-(4-Cyano-phenyl)-3-{[1-(2-fluoro-phenyl)-5-((S)-2-hydroxy-2,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-butyric    acid,-   (S)-3-(2-Fluoro-phenyl)-3-{[1-(2-fluoro-phenyl)-5-((S)-2-hydroxy-2,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic    acid,-   (S)-4-(4-Cyano-phenyl)-3-{[1-(2-fluoro-phenyl)-5-(2-hydroxy-2,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-butyric    acid,-   (S)-3-{[1-(2-Fluoro-phenyl)-5-((S)-2-hydroxy-2,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-4-phenyl-butyric    acid,-   (S)-3-{[1-(2-Fluoro-phenyl)-5-(2-hydroxy-2,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-4-phenyl-butyric    acid,-   (S)-3-(2,3-Dichloro-phenyl)-3-{[5-(3,3-dimethyl-2-oxo-butoxy)-1-(2-fluoro-phenyl)-1H-pyrazole-3-carbonyl]-amino}-propionic    acid,-   (S)-3-{[1-(2-Fluoro-phenyl)-5-((S)-2-hydroxy-2,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-3-(4-methoxy-phenyl)-propionic    acid,-   (S)-3-{[1-(2-Fluoro-phenyl)-5-((S)-2-hydroxy-2,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-5-methyl-hexanoic    acid,-   (S)-3-{[1-(2-Fluoro-phenyl)-5-(2-hydroxy-2,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-5-methyl-hexanoic    acid,-   (1-{[1-(2-Fluoro-phenyl)-5-(2-hydroxy-2,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-cyclopentyl)-acetic    acid,-   (S)-3-(4-Fluoro-phenyl)-3-{[1-(2-fluoro-phenyl)-5-(2-hydroxy-2,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic    acid,-   (S)-3-(2,4-Dimethyl-phenyl)-3-{[1-(2-fluoro-phenyl)-5-(2-hydroxy-2,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic    acid,-   (S)-3-(2-Fluoro-phenyl)-3-{[1-(2-fluoro-phenyl)-5-(2-hydroxy-2,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic    acid,-   (S)-3-(2,3-Dimethoxy-phenyl)-3-{[1-(2-fluoro-phenyl)-5-(2-hydroxy-2,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic    acid,-   (S)-3-{[1-(2-Fluoro-phenyl)-5-(2-hydroxy-2,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-3-(4-methoxy-phenyl)-propionic    acid,-   (S)-3-(2,4-Dichloro-phenyl)-3-{[1-(2-fluoro-phenyl)-5-((S)-2-hydroxy-2,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic    acid,-   (S)-3-{[1-(2-Fluoro-phenyl)-5-((R)-2-hydroxy-2,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-3-(4-methoxy-phenyl)-propionic    acid,-   3-{[1-(2-Fluoro-phenyl)-5-((S)-2-hydroxy-2,3,3-trimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-5-methyl-hexanoic    acid,-   (S)-3-{[1-(2-Fluoro-phenyl)-5-((S)-2-hydroxy-2,3,3-trimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-4-phenyl-butyric    acid,-   (1-{[1-(2-Fluoro-phenyl)-5-((R)-2-hydroxy-2,3,3-trimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-cyclopentyl)-acetic    acid,-   (S)-3-(2-Fluoro-phenyl)-3-{[1-(2-fluoro-phenyl)-5-((R)-2-hydroxy-2,3,3-trimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic    acid,-   (S)-3-(2,3-Dimethoxy-phenyl)-3-{[1-(2-fluoro-phenyl)-5-((R)-2-hydroxy-2,3,3-trimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic    acid,-   (S)-3-{[1-(2-Fluoro-phenyl)-5-((R)-2-hydroxy-2,3,3-trimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-3-(3-methoxy-phenyl)-propionic    acid,-   (S)-3-{[1-(2-Fluoro-phenyl)-5-((R)-2-hydroxy-2,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-3-o-tolyl-propionic    acid,-   (S)-3-{[1-(2-Fluoro-phenyl)-5-((R)-2-hydroxy-2,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-5-methyl-hexanoic    acid,-   (S)-3-(2,4-Dimethyl-phenyl)-3-{[1-(2-fluoro-phenyl)-5-((R)-2-hydroxy-2,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic    acid,-   (S)-3-{[1-(2-Fluoro-phenyl)-5-((R)-2-hydroxy-2,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-3-p-tolyl-propionic    acid,-   (S)-3-(2-Chloro-phenyl)-3-{[1-(2-fluoro-phenyl)-5-((R)-2-hydroxy-2,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic    acid,-   (S)-3-(2-Fluoro-phenyl)-3-{[1-(2-fluoro-phenyl)-5-((R)-2-hydroxy-2,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic    acid,-   (S)-3-{[1-(2-Fluoro-phenyl)-5-((R)-2-hydroxy-2,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-3-(2-trifluoromethyl-phenyl)-propionic    acid,-   (S)-3-{[1-(2-Fluoro-phenyl)-5-((R)-2-hydroxy-2,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-4-phenyl-butyric    acid,-   (S)-3-(3-Cyano-phenyl)-3-{[1-(2-fluoro-phenyl)-5-((R)-2-hydroxy-2,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic    acid,-   (S)-3-(2,3-Dimethoxy-phenyl)-3-{[1-(2-fluoro-phenyl)-5-((R)-2-hydroxy-2,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic    acid,-   (S)-4-(4-Cyano-phenyl)-3-{[1-(2-fluoro-phenyl)-5-((R)-2-hydroxy-2,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-butyric    acid,-   (S)-3-(2,6-Difluoro-phenyl)-3-{[1-(2-fluoro-phenyl)-5-((R)-2-hydroxy-2,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic    acid,-   (S)-3-(3-Fluoro-phenyl)-3-{[1-(2-fluoro-phenyl)-5-((R)-2-hydroxy-2,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic    acid,-   (S)-3-{[1-(2-Fluoro-phenyl)-5-((S)-2-hydroxy-2,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-3-o-tolyl-propionic    acid,-   3-{[1-(2-Fluoro-phenyl)-5-((S)-2-hydroxy-2,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-5-methyl-hexanoic    acid,-   (S)-3-(4-Fluoro-phenyl)-3-{[1-(2-fluoro-phenyl)-5-((S)-2-hydroxy-2,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic    acid,-   (S)-3-(2-Chloro-phenyl)-3-{[1-(2-fluoro-phenyl)-5-((S)-2-hydroxy-2,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic    acid,-   (S)-3-(3-Cyano-phenyl)-3-{[1-(2-fluoro-phenyl)-5-((S)-2-hydroxy-2,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic    acid,-   (S)-3-{[1-(2-Fluoro-phenyl)-5-((S)-2-hydroxy-2,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-3-(3-methoxy-phenyl)-propionic    acid,-   (S)-3-(3-Fluoro-phenyl)-3-{[1-(2-fluoro-phenyl)-5-((S)-2-hydroxy-2,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic    acid,-   (S)-3-(3-Chloro-phenyl)-3-{[1-(2-fluoro-phenyl)-5-((S)-2-hydroxy-2,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic    acid,-   (S)-3-{[1-(2-Fluoro-phenyl)-5-((S)-2-hydroxy-2,3,3-trimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-5-methyl-hexanoic    acid,-   (1-{[1-(2-Fluoro-phenyl)-5-((S)-2-hydroxy-2,3,3-trimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}cyclopentyl)-acetic    acid,-   (S)-3-(4-Fluoro-phenyl)-3-{[1-(2-fluoro-phenyl)-5-((S)-2-hydroxy-2,3,3-trimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic    acid,-   (S)-3-(2,4-Dimethyl-phenyl)-3-{[1-(2-fluoro-phenyl)-5-((S)-2-hydroxy-2,3,3-trimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic    acid,-   (S)-3-(2-Fluoro-phenyl)-3-{[1-(2-fluoro-phenyl)-5-((S)-2-hydroxy-2,3,3-trimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic    acid,-   (S)-3-(2,3-Dimethoxy-phenyl)-3-{[1-(2-fluoro-phenyl)-5-((S)-2-hydroxy-2,3,3-trimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic    acid,-   (S)-3-{[1-(2-Fluoro-phenyl)-5-((S)-2-hydroxy-2,3,3-trimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-3-(3-methoxy-phenyl)-propionic    acid,-   (S)-3-{[1-(2-Fluoro-phenyl)-5-((R)-2-hydroxy-2,3,3-trimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-5-methyl-hexanoic    acid,-   (S)-3-{[1-(2-Fluoro-phenyl)-5-((R)-2-hydroxy-2,3,3-trimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-3-(2-trifluoromethyl-phenyl)-propionic    acid,-   (S)-4-(4-Cyano-phenyl)-3-{[1-(2-fluoro-phenyl)-5-((R)-2-hydroxy-2,3,3-trimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-butyric    acid,-   (S)-3-{[1-(2-Fluoro-phenyl)-5-((R)-2-hydroxy-2,3,3-trimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-3-(4-methoxy-phenyl)-propionic    acid,-   (S)-3-{[1-(2-Fluoro-phenyl)-5-(2-hydroxy-2-phenyl-propoxy)-1H-pyrazole-3-carbonyl]-amino}-3-o-tolyl-propionic    acid,-   1-(2-Fluoro-phenyl)-5-methoxy-1H-pyrazole-3-carboxylic acid    {(S)-2-[(pyridin-2-ylmethyl)-carbamoyl]-1-o-tolyl-ethyl}-amide;    compound with trifluoro-acetic acid,-   1-(2-Fluoro-phenyl)-5-methoxy-1H-pyrazole-3-carboxylic acid    [(S)-2-(cyclopropylmethyl-carbamoyl)-1-o-tolyl-ethyl]-amide,-   1-(2-Fluoro-phenyl)-5-methoxy-1H-pyrazole-3-carboxylic acid    [(S)-2-[(furan-2-yl ethyl)-carbamoyl]-1-o-tolyl-ethyl]-amide,-   1-(2-Fluoro-phenyl)-5-methoxy-1H-pyrazole-3-carboxylic acid    [(S)-2-(3-dimethylamino-propylcarbamoyl)-1-o-tolyl-ethyl]-amide;-   1-(2-Fluoro-phenyl)-5-methoxy-1H-pyrazole-3-carboxylic acid    [(S)-2-(1-ethyl-propylcarbamoyl)-1-o-tolyl-ethyl]-amide,-   1-(2-Fluoro-phenyl)-5-methoxy-1H-pyrazole-3-carboxylic acid    ((S)-2-cyclohexylcarbamoyl-1-o-tolyl-ethyl)amide,-   1-(2-Fluoro-phenyl)-5-methoxy-1H-pyrazole-3-carboxylic acid    [(S)-3-((S)-3-hydroxy-pyrrolidin-1-yl)-3-oxo-1-o-tolyl-propyl]-amide,-   1-(2-Fluoro-phenyl)-5-methoxy-1H-pyrazole-3-carboxylic acid    [(S)-1-o-tolyl-2-((R)-1,2,2-trimethyl-propylcarbamoyl)-ethyl]-amide,-   1-(2-Fluoro-phenyl)-5-methoxy-1H-pyrazole-3-carboxylic acid    [(S)-3-((R)-3-hydroxy-pyrrolidin-1-yl)-3-oxo-1-o-tolyl-propyl]-amide,-   1-(2-Fluoro-phenyl)-5-methoxy-1H-pyrazole-3-carboxylic acid    [(S)-2-((S)-sec-butylcarbamoyl)-1-o-tolyl-ethyl]-amide,-   1-(2-Fluoro-phenyl)-5-methoxy-1H-pyrazole-3-carboxylic acid    [(S)-3-((S)-3-hydroxy-piperidin-1-yl)-3-oxo-1-o-tolyl-propyl]-amide,-   1-(2-Fluoro-phenyl)-5-methoxy-1H-pyrazole-3-carboxylic acid    [(S)-2-(carbamoylmethyl-methyl-carbamoyl)-1-o-tolyl-ethyl]-amide,-   1-(2-Fluoro-phenyl)-5-methoxy-1H-pyrazole-3-carboxylic acid    [(S)-2-((R)-1-cyclopropyl-ethylcarbamoyl)-1-o-tolyl-ethyl]-amide,-   1-(2-Fluoro-phenyl)-5-methoxy-1H-pyrazole-3-carboxylic acid    [(S)-2-((S)-1-cyclopropyl-ethylcarbamoyl)-1-o-tolyl-ethyl]-amide,-   1-(2-Fluoro-phenyl)-5-methoxy-1H-pyrazole-3-carboxylic acid    ((S)-2-cyclobutylcarbamoyl-1-o-tolyl-ethyl)-amide,-   1-(2-Fluoro-phenyl)-5-methoxy-1H-pyrazole-3-carboxylic acid    [(S)-2-[(pyridin-3-ylmethyl)-carbamoyl]-1-o-tolyl-ethyl]-amide;    compound with trifluoro-acetic acid,-   1-(2-Fluoro-phenyl)-5-methoxy-1H-pyrazole-3-carboxylic acid    ((S)-2-cyclopentylcarbamoyl-1-o-tolylethyl)-amide,-   1-(2-Fluoro-phenyl)-5-methoxy-1H-pyrazole-3-carboxylic acid    [(S)-2-(2-methoxy-1-methyl-ethylcarbamoyl)-1-o-tolyl-ethyl]-amide,-   1-(2-Fluoro-phenyl)-5-methoxy-1H-pyrazole-3-carboxylic acid    [(S)-2-(2,2-difluoro-ethylcarbamoyl)-1-o-tolyl-ethyl]-amide,-   1-(2-Fluoro-phenyl)-5-methoxy-1H-pyrazole-3-carboxylic acid    [(S)-1-o-tolyl-2-(2,2,2-trifluoro-ethylcarbamoyl)-ethyl]-amide,-   1-(2-Fluoro-phenyl)-5-methoxy-1H-pyrazole-3-carboxylic acid    [(S)-2-(2-cyclopropyl-ethylcarbamoyl)-1-o-tolyl-ethyl]-amide,-   1-(2-Fluoro-phenyl)-5-methoxy-1H-pyrazole-3-carboxylic acid    {(S)-2-[(pyrimidin-5-ylmethyl)-carbamoyl]-1-o-tolyl-ethyl}-amide,-   1-(2-Fluoro-phenyl)-5-methoxy-1H-pyrazole-3-carboxylic acid    ((S)-2-butylcarbamoyl-1-o-tolyl-ethyl)-amide,-   1-(2-Fluoro-phenyl)-5-methoxy-1H-pyrazole-3-carboxylic acid    {(S)-2-[(furan-3-ylmethyl)-carbamoyl]-1-o-tolyl-ethyl}-amide,-   1-(2-Fluoro-phenyl)-5-methoxy-1H-pyrazole-3-carboxylic acid    {(S)-2-[(pyridin-4-ylmethyl)-carbamoyl]-1-o-tolyl-ethyl}-amide;    compound with trifluoro-acetic acid,-   1-(2-Fluoro-phenyl)-5-methoxy-1H-pyrazole-3-carboxylic acid    [(S)-2-(1,1-dimethyl-propylcarbamoyl)-1-o-tolyl-ethyl]-amide,-   1-(2-Fluoro-phenyl)-5-methoxy-1H-pyrazole-3-carboxylic acid    [(S)-2-((R)-sec-butylcarbamoyl)-1-o-tolyl-ethyl]-amide,-   1-(2-Fluoro-phenyl)-5-methoxy-1H-pyrazole-3-carboxylic acid    ((S)-2-isobutylcarbamoyl-1-o-tolyl-ethyl)-amide,-   1-(2-Fluoro-phenyl)-5-methoxy-1H-pyrazole-3-carboxylic acid    [(S)-1-o-tolyl-2-((S)-1,2,2-trimethyl-propylcarbamoyl)-ethyl]-amide,-   1-(2-Fluoro-phenyl)-5-methoxy-1H-pyrazole-3-carboxylic acid    [(S)-2-(1-methoxymethyl-propylcarbamoyl)-1-o-tolyl-ethyl]-amide,-   1-(2-Fluoro-phenyl)-5-methoxy-1H-pyrazole-3-carboxylic acid    ((S)-2-tert-butylcarbamoyl-1-o-tolyl-ethyl)-amide,-   1-(2-Fluoro-phenyl)-5-methoxy-1H-pyrazole-3-carboxylic acid    [(S)-2-(5-methyl-1H-pyrazol-3-ylcarbamoyl)-1-o-tolyl-ethyl]-amide,-   1-(2-Fluoro-phenyl)-5-methoxy-1H-pyrazole-3-carboxylic acid    [(S)-2-(2,2-dimethyl-propylcarbamoyl)-1-o-tolyl-ethyl]-amide,-   1-(2-Fluoro-phenyl)-5-methoxy-1H-pyrazole-3-carboxylic acid    [(S)-2-(3-hydroxy-2,2-dimethyl-propylcarbamoyl)-1-o-tolyl-ethyl]-amide,-   1-(2-Fluoro-phenyl)-5-methoxy-1H-pyrazole-3-carboxylic acid    [(S)-2-(cyanomethyl-carbamoyl)-1-o-tolyl-ethyl]-amide,-   1-(2-Fluoro-phenyl)-5-methoxy-1H-pyrazole-3-carboxylic acid    [(S)-2-((R)-1-hydroxymethyl-2-methyl-propylcarbamoyl)-1-o-tolyl-ethyl]-amide,-   1-(2-Fluoro-phenyl)-5-methoxy-1H-pyrazole-3-carboxylic acid    ((S)-2-[(1H-tetrazol-5-ylmethyl)-carbamoyl)-1-o-tolyl-ethyl]-amide,-   1-(2-Fluoro-phenyl)-5-methoxy-1H-pyrazole-3-carboxylic acid    ((S)-2-isopropylcarbamoyl-1-o-tolylethyl)-amide,-   1-(2-Fluoro-phenyl)-5-methoxy-1H-pyrazole-3-carboxylic acid    [(S)-2-(1-methyl-1H-pyrazol-3-ylcarbamoyl)-1-o-tolyl-ethyl]-amide,-   1-(2-Fluoro-phenyl)-5-methoxy-1H-pyrazole-3-carboxylic acid    [(S)-2-(2-oxo-pyrrolidin-3-ylcarbamoyl)-1-o-tolyl-ethyl]-amide,-   1-(2-Fluoro-phenyl)-5-methoxy-1H-pyrazole-3-carboxylic acid    [(S)-2-(5-methyl-isoxazol-3-ylcarbamoyl)-1-o-tolyl-ethyl]-amide,-   1-(2-Fluoro-phenyl)-5-methoxy-1H-pyrazole-3-carboxylic acid    ((S)-2-cyclopropylcarbamoyl-1-o-tolyl-ethyl)-amide,-   1-(2-Fluoro-phenyl)-5-methoxy-1H-pyrazole-3-carboxylic acid    {(S)-2-[(isoxazol-5-ylmethyl)-carbamoyl]-1-o-tolyl-ethyl}-amide,-   1-(2-Fluoro-phenyl)-5-methoxy-1H-pyrazole-3-carboxylic acid    [(S)-2-(2-methoxy-ethylcarbamoyl)-1-o-tolyl-ethyl]-amide,-   1-(2-Fluoro-phenyl)-5-methoxy-1H-pyrazole-3-carboxylic acid    [(S)-2-((S)-1-hydroxymethyl-2-methyl-propylcarbamoyl)-1-o-tolyl-ethyl]-amide,-   1-(2-Fluoro-phenyl)-5-methoxy-1H-pyrazole-3-carboxylic acid    [(S)-2-((S)-2-methoxy-1-methyl-ethylcarbamoyl)-1-o-tolyl-ethyl]-amide,-   1-(2-Fluoro-phenyl)-5-methoxy-1H-pyrazole-3-carboxylic acid    ((S)-2-{[(S)-1-(tetrahydro-furan-2-yl)methyl]-carbamoyl}-1-o-tolyl-ethyl)-amide    and 1-(2-Fluoro-phenyl)-5-methoxy-1H-pyrazole-3-carboxylic acid    [(S)-2-((R)-1,2-dimethyl-propylcarbamoyl)-1-o-tolyl-ethyl]-amide,-   or which is any one of these compounds, or a physiologically    acceptable salt thereof, or a physiologically acceptable solvate of    any of them, wherein the compound of the formula I is a subject of    the invention in any of its stereoisomeric forms or a mixture of    stereoisomeric forms in any ratio, unless a specific stereoisomeric    form is specified with respect to any carbon atoms in the respective    compound.

Another subject of the present invention are processes for thepreparation of the compounds of the formula I which are outlined belowand by which the compounds are obtainable. For example, the preparationof the compounds of the formula I can be carried out by reacting acompound of the formula II with a compound of the formula III withformation of an amide bond. Various synthetic methods for the formationof the amide bond are described in C. A. G. N. Montalbetti et al.,Tetrahedron 61 (2005), 10827-10852, for example.

The groups A, D, E, G, R¹⁰, R³⁰, R⁴⁰, R⁵⁰ and R⁶⁰ in the compounds ofthe formulae II and III are defined as in the compounds of the formula Iand additionally functional groups can be present in protected form orin the form of a precursor group which is later converted into the finalgroup. The group J in the compounds of the formula II can be HO—(hydroxy), i.e. the compound of the formula II can thus be a carboxylicacid, or another group which can be replaced by the group NH in thecompound of the formula III in a substitution reaction, for example anaryloxy group such as optionally substituted phenoxy or an alkyloxygroup such as a (C₁-C₄)-alkyl-O— group, for example a (C₁-C₃)-alkyl-O—group like methoxy or ethoxy, or halogen, for example chlorine orbromine, and the compound of the formula II can thus be a reactive esterlike an aryl ester or alkyl ester, for example a methyl ester or ethylester, or an acid halide, for example an acid chloride or acid bromide,of the respective carboxylic acid. The compounds of the formulae II andIII can also be employed, and the compounds of the formula I obtained,in the form of a salt, for example an acid addition salt such as anhydrohalide, for example a hydrochloride, of the compound of the formulaIII and/or an alkaline metal salt, for example a sodium salt, of acompound of the formula II in which J is HO—. Likewise, in all otherreactions in the preparation of the compounds of the formula I,including the preparation of starting compounds, compounds can also beemployed and/or products obtained in the form a salt.

In case a compound of the formula II is employed in which J is HO—, thecarboxylic acid group HO—C(O)— is generally activated in situ by meansof a customary amide coupling reagent or converted into a reactivecarboxylic acid derivative which can be prepared in situ or isolated.For example, the compound of the formula II in which J is HO— can beconverted into an acid halide, such as the compound of the formula II inwhich J is chlorine or bromine, by treatment with thionyl chloride,phosphorus pentachloride, phosphorus tribromide or oxalyl chloride, ortreated with an alkyl chloroformate like ethyl chloroformate or isobutylchloroformate to give a mixed anhydride. In a favorable method for theconversion into the acid chloride, the acid is treated with oxalylchloride in the presence of a catalytic amount of an amide such asN,N-dimethylformamide in an inert solvent such as a hydrocarbon orchlorinated hydrocarbon or an ether, at temperatures from about 0° C. toabout 60° C., for example at room temperature. Customary amide couplingreagents which can be employed, are propanephosphonic anhydride,N,N′-carbonyldiazoles like N,N′-carbonyldiimidazole (CU), carbodiimideslike 1,3-diisopropylcarbodiimide (DIC), 1,3-dicyclohexylcarbodiimide(DCC) or 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride(EDC), carbodiimides together with additives like1-hydroxy-benzotriazole (HOBT) or 1-hydroxy-7-azabenzotriazole (HOAT),uronium-based coupling reagents likeO—(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluroniumhexafluorophosphate (HATU),O-(benzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate(HBTU) orO-(cyano(ethoxycarbonyl)methyleneamino)-N,N,N′,N′-tetramethyluroniumtetrafluoroborate (TOTU), and phosphonium-based coupling reagents like(benzotriazol-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate(BOP), (benzotriazol-1-yloxy)tripyrrolidinophosphoniumhexafluorophosphate (PyBOP) or bromotripyrrolidinophosphoniumhexafluorophosphate (PyBroP).

The reaction conditions for the preparation of the compounds of theformula I from compounds of the formulae II and III depend on theparticulars of the specific case, for example the meaning of the group Jor the employed coupling reagent, and are familiar to a skilled personin view of the general knowledge in the art. For example, in case acompound of the formula II in which J is alkyl-O—, like methoxy orethoxy, is reacted with a compound of the formula III, generally thereaction is carried out in an inert solvent, for example a hydrocarbonor chlorinated hydrocarbon like benzene, toluene, xylene, chlorobenzene,dichloromethane, chloroform or dichloroethane, an ether liketetrahydrofuran (THF), 2-methyltetrahydrofuran, dioxane, dibutyl ether,diisopropyl ether or dimethoxyethane (DME), or a mixture of solvents, atelevated temperatures, for example at temperatures from about 40° C. toabout 140° C., in particular at temperatures from about 50° C. to about120° C., for example at about the boiling temperature of the solvent. Incase a compound of the formula II in which J is halogen, like chlorineor bromine, is reacted with a compound of the formula III, generally thereaction is likewise carried out in an inert solvent, for example ahydrocarbon or chlorinated hydrocarbon or ether like the aforementionedones, an ester like ethyl acetate or butyl acetate, a nitrile likeacetonitrile, or water, or a mixture of solvents including a mixture ofwater and an organic solvent which is miscible or immiscible with water,at temperatures from about −10° C. to about 100° C., in particular attemperatures from about 0° C. to about 80° C., for example at about roomtemperature. Favorably, the reaction of a compound of the formula II inwhich J is halogen with a compound of the formula III is carried out inthe presence of a base such as a tertiary amine, like triethylamine,N-ethyl-diisopropylamine (EDIA), N-methylmorpholine, N-ethylmorpholineor pyridine, or an inorganic base such as an alkaline metal hydroxide,carbonate or hydrogencarbonate, like sodium hydroxide, potassiumhydroxide, sodium carbonate or sodium hydrogencarbonate.

In case a compound of the formula II in which J is HO— is reacted with acompound of the formula III and the carboxylic acid group is activatedby means of an amide coupling reagent such as, for example, acarbodiimide or TOTU, the reaction is generally carried out underanhydrous conditions in an inert aprotic solvent, for example an etherlike THF, dioxane or DME, an amide like N,N-dimethylformamide (DMF) orN-methylpyrrolidone (NMP), at temperatures from about −10° C. to about40° C., in particular at temperatures from about 0° C. to about 30° C.,for example at room temperature, in the presence of a base such as atertiary amine, like triethylamine, EDIA, N-methylmorpholine orN-ethylmorpholine. In case the compound of the formula III is employedin the form of an acid addition salt in the reaction with the compoundof the formula II, usually a sufficient amount of a base is added inorder to liberate the free compound of the formula III.

As indicated above, during the formation of the amide bond between thecompounds of the formulae II and III functional groups in the compoundsof the formulae II and III can be present in protected form or in theform of a precursor group. Depending on the particulars of the specificcase, it may be necessary or advisable for avoiding an undesired courseof the reaction or side reactions to temporarily block any functionalgroups by protective groups and remove them later, or to let functionalgroups be present in the form of a precursor group which is laterconverted into the desired final group. This applies correspondingly toall reactions in the course of the synthesis of the compounds of theformula I including the synthesis of intermediates, starting compoundsand building blocks. Respective synthetic strategies are commonly usedin the art. Details about protective groups and their introduction andremoval are described in P. G. M. Wuts and T. W. Greene, Greene'sProtective Groups in Organic Synthesis, 4. ed. (2007), John Wiley &Sons, for example. Examples of protective groups which may be mentioned,are benzyl protective groups which may occur in the form of benzylethers of hydroxy groups and benzyl esters of carboxylic acid groupsfrom which the benzyl group can be removed by catalytic hydrogenation inthe presence of a palladium catalyst, tert-butyl protective groups whichmay occur in the form of tert-butyl esters of carboxylic acid groupsfrom which the tert-butyl group can be removed by treatment withtrifluoroacetic acid, acyl protective groups which may be used toprotect hydroxy groups and amino groups in the form of esters and amidesand which can be cleaved by acidic or basic hydrolysis, andalkyloxycarbonyl protective groups which may occur in the form oftert-butoxycarbonyl derivatives of amino groups which can be cleaved bytreatment with trifluoroacetic acid. Undesired reactions of carboxylicacid groups, for example the carboxylic acid group present in thecompound of the formula III in case G is a carboxylic acid group in thedesired compound of the formula I, can also be avoided by employing themin the reaction with the compounds of the formula II in the form ofother esters, for example in the form of alkyl esters like the methyl orethyl ester which can be cleaved by hydrolysis, for example by means ofan alkaline metal hydroxide like sodium hydroxide or lithium hydroxide.As examples of a precursor group, the cyano group (NC—, N≡C—) may bementioned which can be converted into a carboxylic acid group, acarboxylic acid ester group and a carboxamide group under hydrolyticconditions or into a aminomethyl group by reduction, and the nitro groupwhich can be converted into an amino group by reduction, for example bycatalytic hydrogenation or by reduction with sodium dithionite, forexample. A further example of a precursor group is an oxo group, whichmay initially be present in the course of the synthesis of compounds ofthe formula I containing a hydroxy group, and which can be reduced, forexample with a complex hydride such as sodium borohydride, or reactedwith an organometallic compound, for example a Grignard compound. If anyprotective groups or precursor groups are present in the compounds ofthe formulae II and III and the direct product of the reaction is notyet the desired final compound, the removal of the protective group orconversion into the desired compound can in general also be carried outin situ.

The starting compounds for the synthesis of the compounds of the formulaI can generally be prepared according to procedures described in theliterature or analogously to such procedures, or are commerciallyavailable. As an example of the synthesis of compounds of the formulaII, synthetic procedures for the synthesis of compounds of the formulaII in which A is C(R¹), D is N(R²) and E is N, i.e. of5-oxygen-substituted pyrazole-3-carboxylic acids and acid derivatives,are outlined in the following. In one such procedure, oxalacetic acid ofthe formula IV is reacted with a substituted hydrazine of the formula Vin a solvent such as water in the presence of an acid, such as sulfuricacid, hydrochloric acid or acetic acid, to give a5-hydroxy-pyrazole-3-carboxylic acid of the formula IIa in which R andR¹ are hydrogen and which can then be reacted with a compound of theformula III.

In a similar manner can diethyl oxalacetate, i.e. the compound of theformula VI in which R¹ is hydrogen and R′ is ethyl, be reacted with asubstituted hydrazine to give a compound of the formula IIa in which R¹is hydrogen and R is ethyl, and can substituted oxalylacetates, forexample compounds of the formula VI in which R¹ is an alkyl group suchas methyl or ethyl and R′ is ethyl, be reacted with a substitutedhydrazine, for example by heating the components and/or treating themwith a base such as an alkaline metal hydroxide like sodium hydroxide orpotassium hydroxide, to give a compound of the formula IIa in which R¹is hydrogen or has another meaning than hydrogen, respectively, and R isan alkyl group, as described in S. Sugiura et al., J. Med. Chem. 20(1997), 80-85; P. E. Gagnon et al., Can. J. Chem. 30 (1952), 904-914; orJP 2000/169453, for example. Compounds of the formula IIa, in which R¹is hydrogen and R is an alkyl group such as methyl, can also be preparedby reaction of an acetylenedicarboxylate of the formula VII, for exampledimethyl acetylenedicarboxylate, with a hydrazine derivative in asolvent such as an alcohol like methanol in the presence of a base suchas a tertiary amine, for example triethylamine or EDIA (cf. E. Buchner,Chem. Ber. 22 (1889), 2929-2932). The groups R¹ and R² in the compoundsof the formulae IIa, V and VI are defined as in the compounds of theformula I and additionally functional groups can be present in protectedform or in the form of a precursor group which is later converted intothe final group. Depending on the individual case, in these proceduresR¹ is in particular hydrogen or a group such as (C₁-C₆)-alkyl, forexample methyl or ethyl, and R² is in particular an aromatic group suchas an optionally substituted phenyl group or aromatic heterocyclicgroup. The group R′ in the compounds of the formulae VI and VII is(C₁-C₄)-alkyl, for example methyl or ethyl. As indicated, the group R inthe compounds of the formula IIa can be hydrogen or (C₁-C₄)-alkyl, forexample methyl or ethyl. The compounds of the formula IIa, as well asother suitable compounds occurring in the synthesis of the compounds ofthe formula I and the compounds of the formula I themselves, can also bepresent in other tautomeric forms, in particular the form in which thehydroxy group in 5-position is present as an oxo group and the ringnitrogen atom in 2-position carries a hydrogen atom.

If desired for the intended use of the compound of the formula IIa inthe synthesis of the compound of the formula I, a compound of theformula IIa in which R is hydrogen, i.e. a carboxylic acid, can easilybe converted into a compound of the formula IIa in which is R is(C₁-C₄)-alkyl, or into another carboxylic acid ester, as well as acompound of the formula IIa is (C₁-C₄)-alkyl can be converted into acompound of the formula IIa in which R is hydrogen. Such conversions canbe performed under standard conditions which are well known to a personskilled in the art. For example, an esterification of a carboxylic acidto give an ester such as a methyl or ethyl ester can be performed bytreating the carboxylic acid in the respective alcohol as solvent withan acid like hydrogen chloride or with thionyl chloride, and asaponification of a carboxylic acid ester such as a methyl or ethylester to give the carboxylic acid can be performed by treating the esterin a solvent such as an alcohol like methanol or ethanol, an ether likeTHF or dioxane, or a ketone like methyl isobutyl ketone, or a mixturethereof in the presence of water with a base such as an alkaline metalhydroxide like sodium hydroxide or lithium hydroxide. This applies justso to carboxylic acid groups and carboxylic acid ester groups in othercompounds occurring in the synthesis of the compounds of the formula I.

Compounds of the formula IIa can readily be converted into compounds ofthe formula IIb, which are substituted on the hydroxy group in5-position and which can likewise be reacted with a compound of theformula III, by reaction with an electrophilic reagent of the formulaVIII.

The groups R¹, R² and R in the compounds of the formula IIb are definedas in the compounds of the formula IIb. The group R^(10a) in thecompounds of the formulae IIb and VIII is chosen from the seriesconsisting R¹¹, R¹²—N(R¹³)—C(O)— and Het²—C(O)— wherein R¹¹, R¹². R¹³and Het² are defined as in the compounds of the formula I, except thatR¹¹ is not hydrogen, and additionally functional groups can be presentin protected form or in the form of a precursor group which is laterconverted into the final group, i.e. the group R^(10a)—O— issubstantially defined as the group R¹⁰ in the compounds of the formulaI, except that it is not a hydroxy group. The group L in the compoundsof the formula VIII is a nucleophilically substitutable leaving groupwhich can be replaced by the oxygen atom of the hydroxy group in thecompound of the formula IIa in the respective reaction type, for examplehalogen such as fluorine, chlorine, bromine or iodine, or a sulfonyloxygroup such as methanesulfonyloxy, trifluoromethanesulfonyloxy,toluenesulfonyloxy, methoxysulfonyloxy or ethoxysulfonyloxy, or L canalso be a hydroxy group and in the latter case the compounds of theformulae IIa and VIII reacted under the conditions of the Mitsunobureaction, for example.

In case the group R^(10a) is R¹²—N(R¹³)—C(O)— or Het²—C(O)—, the group Lin the respective compounds of the formula VIII advantageously ischlorine and the compound of the formula VIII thus is an acyclic orcyclic carbamyl chloride. The reaction of such a compound of the formulaVIII with a compound of the formula IIa is generally carried out in aninert solvent, for example a hydrocarbon or a chlorinated hydrocarbonlike toluene, dichloromethane or dichloroethane, an ether like THF ordioxane, in the presence of a base such as an amine like triethylamineor EDIA, or an inorganic base like a basic alkaline metal salt, forexample a carbonate like sodium carbonate or cesium carbonate, attemperatures from about 0° C. to about 80° C., in particular from about20° C. to about 60° C.

In case the group R^(10a) in the compound of the formula VIII is R¹¹,the group R¹¹ is a group such as alkyl, for example, the group L ishalogen or a sulfonyloxy group and the compound of the formula VIII thusis an alkyl halide, an alkyl sulfonate or a dialkyl sulfate, or arespective compound of another type, the reaction of the compounds ofthe formulae IIa and VIII is an O-alkylation and constitutes anucleophilic substitution reaction. Suitable conditions for such areaction are well known to a person skilled in the art and haveextensively been described in the literature, for example in S. Sugiuraet al., J. Med. Chem. 80 (1977), 80-85; W.-M. Liu et al., J. Heterocycl.Chem. 44 (2007), 967-971; or U.S. Pat. No. 5,258,397. Generally thereaction is carried out in an inert solvent, for example a hydrocarbonor chlorinated hydrocarbon such as benzene, toluene, chlorobenzene,dichloromethane, chloroform or dichloroethane, an ether such as THF,dioxane, dibutyl ether, diisopropyl ether or DME, an alcohol such asmethanol, ethanol or isopropanol, a ketone such as acetone, butan-2-oneor methyl isobutyl ketone, an ester such as ethyl acetate or butylacetate, a nitrile such acetonitrile, an amide such as DMF or NMP, or amixture of solvents, including two-phasic mixtures with aqueoussolutions, at temperatures from about −20° C. to about 100° C., forexample at temperatures from about 0° C. to about 80° C., depending onthe particulars of the specific case. The reaction can also be carriedout in the presence of an ionic liquid. Generally it is favorable forenhancing the nucleophilicity of the compound of the formula IIa and/orbinding an acid which is liberated during the reaction, to add a base,for example a tertiary amine, such as triethylamine, EDIA orN-methylmorpholine, or an inorganic base such as an alkaline metalhydride, hydroxide, carbonate or hydrogencarbonate like sodium hydride,sodium hydroxide, potassium hydroxide, sodium carbonate, potassiumcarbonate, cesium carbonate or sodium hydrogencarbonate, or an alkoxideor amide such as sodium methoxide, sodium ethoxide, potassium methoxide,potassium tert-butoxide, sodium amide or lithium diisopropylamide,wherein a compound of the formula IIa can also be treated with a baseseparately before the reaction with the compound of the formula VIII. Bythe choice of the reaction conditions, such as the solvent and the base,as well as the choice of the group L in the compound of the formulaVIII, which compound can in the case that R^(10a) is methyl be a halidesuch as iodomethane or bromomethane, a sulfonate such as methyltosylate, or a sulfate such as dimethyl sulfate, for example, it is alsopossible to control the regioselectivity of the reaction with thecompound of the formula IIa which reaction can, besides on the oxygenatom of the hydroxy group in 5-position, also occur on the ring nitrogenatom in 2-position, as is known to a person skilled in the art. If acompound of the formula IIa in which R is hydrogen, is reacted with acompound of the formula VIII in which R^(10a) is R¹¹, besides on thehydroxy group in 5-position can a reaction with the compound of theformula VIII also occur on the carboxylic acid group, and the latter canbe converted into an ester. For the subsequent reaction step, such anester group can be converted in the carboxylic acid, as outlined above.

In case the group R^(10a) in the compound of the formula VIII is R¹¹,the group R¹¹ is a group such as alkyl, for example, the group L ishydroxy and the compound of the formula VIII thus is an alkanol, or arespective compound of another type, the reaction of the compounds ofthe formulae IIa and VIII can be performed under the conditions of theMitsunobu reaction, as mentioned above. The Mitsunobu reaction isgenerally performed in an inert solvent, such as a hydrocarbon orchlorinated hydrocarbon like toluene or dichloromethane, or an etherlike THF or dioxane, in the presence of an azodicarboxylate such asdiethyl azodicarboxylate, diisopropyl azodicarboxylate ordi(4-chlorobenzyl) azodicarboxylate, and a phosphine such astriphenylphosphine or tributylphosphine, at temperatures from about 0°C. to about 40° C., for example at about room temperature (cf. O.Mitsunobu, Synthesis (1981), 1-28).

Compounds of the formula II for use in the synthesis of compounds of theformula I in which the groups A, D and E have other meanings than in thecompounds of the formulae IIa and IIb which are exemplarily discussedabove, can likewise be prepared according to procedures, or analogouslyto procedures, which are described in the literature and are generallyknown to a person skilled in the art, the synthetic strategy in aspecific case being dependent on the kind of the heterocycle. Forexample, a procedure for the synthesis of compounds of the formula II inwhich A is N, D is N(R²) and E is N, i.e. of 5-oxygen-substituted[1,2,4]triazole-3-carboxylic acid derivatives, which comprises thealcoholysis of 2-imino-1,3,4-oxadiazole derivatives, is described in DD226883. The oxadiazole derivatives may be obtained from acylhydrazinesby reaction with a cyanate as described in M. Neitzel et al., Arch.Pharm. 313 (1980), 867-878. A procedure for the synthesis of compoundsof the formula II in which A is N, D is N(R²) and E is C(R³), i.e. of2-oxygen-substituted imidazole-4-carboxylic acid derivatives, whichcomprises the reaction of an alpha-diazo-beta-ketoester with asubstituted urea in the presence of a rhodium catalyst, is described inS.-H. Lee et al., Org. Lett. 5 (2003), 511-514 and WO 2008/139941. Thehydroxy group in the 2-position of the obtained imidazole derivative canthen by alkylated with triethyloxonium tetrafluoroborate, for example. Aprocedure for the synthesis of compounds of the formula II in which A isC(R¹), D is N(R²) and E is C(R³), i.e. of 5-oxygen-substitutedpyrrole-3-carboxylic acid derivatives, which comprises the reaction ofan alpha-dicarbonyl compound with an N-substituted beta-amino-acrylicacid ester, is described in E. Caballero et al., Tetrahedron 50 (1994),7849-7865. A procedure for the synthesis of compounds of the formula IIin which A is N, D is O and E is C(R³), i.e. of 2-oxygen-substituted[1,3]oxazole-4-carboxylic acid derivatives, which comprises the exchangeof the chlorine atom in ethyl 2-chloro-oxazole-3-carboxylate with anoxygen substituent, is described in G. L. Young et al., TetrahedronLett. 45 (2004), 3797-3801; and WO 2007/000582. The2-chloro-oxazole-3-carboxylate may be obtained by condensation of ethylbromopyruvate and urea, diazotation of the obtained 2-amino-oxazolederivative and treatment with copper chloride as described in K. J.Hodgetts et al., Org. Lett. 4 (2002), 2905-2907. A similar procedure forthe synthesis of compounds of the formula II in which A is N, D is S andE is C(R³), i.e. of 2-oxygen-substituted [1,3]thiazole-4-carboxylic acidderivatives, which comprises the exchange of the bromine atom in ethyl2-bromo-thiazole-3-carboxylates, which may be obtained fromhalo-pyruvates by condensation with thiourea and diazotation of theobtained 2-amino-thiazole derivative and treatment with a copper bromideas is also described in T. R. Kelly et al., J. Org. Chem. 61 (1996),4623-4633, with an oxygen substituent, is described in WO 94/27983; WO02/14311 and WO 2009/104155. Likewise further compounds of the formulaII can be prepared.

The β-amino acids and derivatives of the formula III are commerciallyavailable or can be synthesized by well-known standard methods, oranalogously to such methods, from readily available starting compounds.For example, for the preparation of β-amino acids and their alkyl estersof the formula III in which R⁵⁰ and R⁶⁰ are hydrogen, can carbonylcompounds of the formula R³⁰—C(O)—R⁴⁰, in particular aldehydes of theformula R³²—C(O)—H, be reacted with malonic acid mono-ethyl ester andammonia in the presence of a base such as an alkaline metal hydroxidelike potassium hydroxide in a solvent such as an alcohol like ethanol,as described in V. M. Rodionov et al., Izv. Akad. Nauk SSSR, Ser. Khim.(1952), 696-702 (Chem. Abstr. 47 (1953), abstr. no. 61888), or ammoniaadded to the double bond in the condensation product of the carbonylcompound with malonic acid or diethyl malonate and in the case of thecondensation product with diethyl malonate the reaction product treatedwith an acid such as hydrochloric acid, as described in V. Scudi, J. Am.Chem. Soc. 57 (1935), 1279; or M. K. Tse et al., Chem. Eur. J. 12(2006), 1855-1874, and in the obtained product an ester group hydrolyzedto the carboxylic acid, or a carboxylic acid group esterified,respectively, as desired and outlined above. Enantiomerically pure suchcompounds of the formula III, for example, can be obtained from theracemic compounds by crystallization of a salt with an optically activeacid, such as tartaric acid, by stereoselective enzymatic or microbialdegradation, for example as described in the mentioned article by M. K.Tse et al., or in J. Mano et al., Bioscience, Biotechnology andBiochemistry 70 (2006), 1941-1946. In another strategy for the synthesisof such compounds, in particular compounds in which R⁴⁰, R⁵⁰ and R⁶⁰ arehydrogen and R³⁰ is R³², the respective 3-substituted acrylic acid,which can be obtained from the corresponding aldehyde, is converted intothe acid chloride, for example with oxalyl chloride, and the acidchloride converted with an alcohol into an ester, for example into thetert-butyl ester using tert-butanol, and the amino group is thenintroduced by reaction with the lithium salt of an optically activeamine, for example the lithium salt of(R)-(+)-N-benzyl-N-(1-phenylethyl)amine, and in the obtained3-substituted tert-butyl 3-(N-benzyl-N-(1-phenylethyl)amino)propionatethe benzyl group and the phenylethyl group is cleaved off by means ofcatalytic hydrogenation (cf. S. G. Davies et al., Tetrahedron: Asymmetry2 (1991), 183-186); S. G. Davies et al., J. Chem. Soc. Perkin Trans. 1(1994), 1129-1139).

The introduction of the structural moieties of the compounds of theformula in the course of the synthesis can also occur in another orderthan outlined above. For example, in the case of compounds of theformula I in which R¹⁰ is another group than hydroxy, instead ofpreparing a compound of the formula II which contains the group R¹⁰ andreacting it with a compound of the formula III, also a compound of theformula IIc, which specifically comprises a hydroxy group in place ofthe group R¹⁰, can be reacted with a compound of the formula III, andthe obtained compound of the formula Ia then modified on the hydroxygroup by reaction with a compound of the formula VIII to give a compoundof the formula I in which R¹⁰ is different from hydroxy, i.e. a compoundof the formula Ib. At the end, like in the compounds of the formula Iwhen prepared as outlined above, any protective groups in the compoundsof the formula Ib may still be deprotected and/or precursor groupconverted into the final groups.

The groups A, D, E, G, R³⁰, R⁴⁰, R⁵⁰ and R⁶⁰ in the compounds of theformulae Ia, Ib and IIc are defined as in the compounds of the formula Iand additionally functional groups can be present in protected form orin the form of a precursor group which is later converted into the finalgroup. The group J in the compounds of the formula IIc is defined as inthe compounds of the formula II. The group R^(10a) in the compounds ofthe formula Ib is defined as in the compounds of the formulae IIb andVIII. The explanations given above on the reaction of the compounds ofthe formulae II and III and the reaction of the compounds of theformulae IIa and VIII apply correspondingly to the reaction of thecompounds of the formulae IIc and III and the reaction of the compoundsIa and VIII, respectively.

For obtaining further compounds of the formula I, varioustransformations of functional groups can be carried out under standardconditions in compounds of the formula I or intermediates or startingcompounds of the synthesis of the compounds of the formula I. Forexample, a hydroxy group, including a hydroxy group representing R¹⁰ ina compound of the formula I, can be etherified, as outlined above, forexample by alkylation with a halogen compound, for example a bromide oriodide, in the presence of a base such an alkali metal carbonate likepotassium carbonate or cesium carbonate in an inert solvent such as anamide like DMF or NMP or a ketone like acetone or butan-2-one, or withthe respective alcohol under the conditions of the Mitsunobu reactionreferred to above. A hydroxy group can be esterified to give acarboxylic acid ester or a sulfonic acid ester, or converted into ahalide by treatment with a halogenating agent. Halogen atoms can also beintroduced by means of suitable halogenating agents which replace ahydrogen atom in the starting compound, for example by means ofelemental bromine, sulfuryl chloride or1-chloromethyl-4-fluoro-1,4-diazoniabicyclo[2.2.2]octanebis(tetrafluoroborate), which introduce a bromine, chlorine and fluorinesubstituent, respectively, for example in the 4-position of a compoundof the formula IIb. A halogen atom can generally be replaced with avariety of groups in substitution reactions which may also betransition-metal catalyzed reactions. A nitro group can be reduced to anamino group, for example by catalytic hydrogenation. An amino group canbe modified under standard conditions for alkylation, for example byreaction with a halogen compound or by reductive amination of a carbonylcompound, or for acylation or sulfonylation, for example by reactionwith an activated carboxylic acid or a carboxylic acid derivate like anacid chloride or anhydride or a sulfonic acid chloride. A carboxylicester group can be hydrolyzed under acidic or basic conditions to give acarboxylic acid. An acid group can be activated or converted into areactive derivative as outlined above and reacted with an alcohol or anamine or ammonia to give an ester or amide. A primary amide can bedehydrated to give a nitrile. A sulfur atom in an alkyl-S— group or in aheterocyclic ring can be oxidized with a peroxide like hydrogen peroxideor a peracid to give a sulfoxide moiety S(O) or a sulfone moiety S(O)₂.A carboxylic acid group, carboxylic acid ester group and a ketone groupcan be reduced to an alcohol, for example with a complex hydride such allithium aluminium hydride, lithium borohydride or sodium borohydride, orreacted with an organometallic compound or a Grignard compound to givean alcohol. Primary and secondary hydroxy groups can also be oxidized tothe oxo groups. All reactions in the preparation of the compounds of theformula I are known per se and can be carried out in a manner familiarto a person skilled in the art according to, or analogously to,procedures which are described in the standard literature, for examplein Houben-Weyl, Methods of Organic Chemistry, Thieme; or OrganicReactions, John Wiley & Sons; or R. C. Larock, Comprehensive OrganicTransformations: A Guide to Functional Group Preparations, 2. ed.(1999), John Wiley & Sons, and the references quoted therein.

Another subject of the present invention are the novel startingcompounds and intermediates occurring in the synthesis of the compoundsof the formula I, including the compounds of the formulae Ia, Ib, II,IIa, IIb, IIc, III, V, VI and VIII, wherein the groups A, D, E, G, J, L,R², R¹⁰, R^(10a), R³⁰, R⁴⁰, R⁵⁰ and R⁶⁰ are defined as above, in any oftheir stereoisomeric forms or a mixture of stereoisomeric forms in anyratio, and their salts, and solvates of any of them, and their use assynthetic intermediates or starting compounds. All general explanations,specifications of embodiments and definitions of numbers and groupsgiven above with respect to the compounds of the formula I applycorrespondingly to the said intermediates and starting compounds. Asubject of the invention are in particular the novel specific startingcompounds and intermediates described herein. Independently thereofwhether they are described as a free compound and/or as a specific salt,they are a subject of the invention both in the form of the freecompounds and in the form of their salts, and if a specific salt isdescribed, additionally in the form of this specific salt.

The compounds of the formula I inhibit the protease cathepsin A as canbe demonstrated in the pharmacological test described below and in othertests which are known to a person skilled in the art. The compounds ofthe formula I and their physiologically acceptable salts and solvatestherefore are valuable pharmaceutical active compounds. The compounds ofthe formula I and their physiologically acceptable salts and solvatescan be used for the treatment of cardiovascular diseases such as heartfailure including systolic heart failure, diastolic heart failure,diabetic heart failure and heart failure with preserved ejectionfraction, cardiomyopathy, myocardial infarction, left ventriculardysfunction including left ventricular dysfunction after myocardialinfarction, cardiac hypertrophy, myocardial remodeling includingmyocardial remodeling after infarction or after cardiac surgery,valvular heart diseases, vascular hypertrophy, vascular remodelingincluding vascular stiffness, hypertension including pulmonaryhypertension, portal hypertension and systolic hypertension,atherosclerosis, peripheral arterial occlusive disease (PAOD),restenosis, thrombosis and vascular permeability disorders, ischemiaand/or reperfusion damage including ischemia and/or reperfusion damageof the heart and ischemia and/or reperfusion damage of the retina,inflammation and inflammatory diseases such as rheumatoid arthritis andosteoarthritis, renal diseases such as renal papillary necrosis andrenal failure including renal failure after ischemia/reperfusion,pulmonary diseases such as cystic fibrosis, chronic bronchitis, chronicobstructive pulmonary disease (COPD), asthma, acute respiratory distresssyndrome (ARDS), respiratory tract infections and lung carcinoma,immunological diseases, diabetic complications including diabeticnephropathy and diabetic cardiomyopathy, fibrotic diseases such aspulmonary fibrosis including idiopathic lung fibrosis, cardiac fibrosis,vascular fibrosis, perivascular fibrosis, renal fibrosis including renaltubulointerstitial fibrosis, fibrosing skin conditions including keloidformation, collagenosis and scleroderma, and liver fibrosis, liverdiseases such as liver cirrhosis, pain such as neuropathic pain,diabetic pain and inflammatory pain, macular degeneration,neurodegenerative diseases or psychiatric disorders, or forcardioprotection including cardioprotection after myocardial infarctionand after cardiac surgery, or for renoprotection, for example. Thecompounds of the formula I and their physiologically acceptable saltsand solvates can be used as diuretic (stand-alone treatment or incombination with established diuretics). The treatment of diseases is tobe understood as meaning both the therapy of existing pathologicalchanges or malfunctions of the organism or of existing symptoms with theaim of relief, alleviation or cure, and the prophylaxis or prevention ofpathological changes or malfunctions of the organism or of symptoms inhumans or animals which are susceptible thereto and are in need of sucha prophylaxis or prevention, with the aim of a prevention or suppressionof their occurrence or of an attenuation in the case of theiroccurrence. For example, in patients who on account of their diseasehistory are susceptible to myocardial infarction, by means of theprophylactic or preventive medicinal treatment the occurrence orre-occurrence of a myocardial infarction can be prevented or its extentand sequalae decreased, or in patients who are susceptible to attacks ofasthma, by means of the prophylactic or preventive medicinal treatmentsuch attacks can be prevented or their severity decreased. The treatmentof diseases can occur both in acute cases and in chronic cases. Theefficacy of the compounds of the formula I can be demonstrated in thepharmacological test described below and in other tests which are knownto a person skilled in the art. The compounds of the formula I with Gselected from R⁷²—N(R⁷³)—C(O)— and their physiologically acceptablesalts and solvates can also be used as prodrugs.

The compounds of the formula I and their physiologically acceptablesalts and solvates can therefore be used in animals, in particular inmammals and specifically in humans, as a pharmaceutical or medicament ontheir own, in mixtures with one another or in the form of pharmaceuticalcompositions. A subject of the present invention also are the compoundsof the formula I and their physiologically acceptable salts and solvatesfor use as a pharmaceutical, as well as pharmaceutical compositions andmedicaments which comprise an efficacious dose of at least one compoundof the formula I and/or a physiologically acceptable salt thereof and/orsolvate thereof as an active ingredient and a pharmaceuticallyacceptable carrier, i.e. one or more pharmaceutically innocuous, ornonhazardous, vehicles and/or excipients, and optionally one or moreother pharmaceutical active compounds. A subject of the presentinvention furthermore are the compounds of the formula I and theirphysiologically acceptable salts and solvates for use in the treatmentof the diseases mentioned above or below, including the treatment of anyone of the mentioned diseases, for example the treatment of heartfailure, myocardial infarction, cardiac hypertrophy, diabeticnephropathy, diabetic cardiomyopathy, cardiac fibrosis, or ischemiaand/or reperfusion damage, or for cardioprotection, the use of thecompounds of the formula I and their physiologically acceptable saltsand solvates for the manufacture of a medicament for the treatment ofthe diseases mentioned above or below, including the treatment of anyone of the mentioned diseases, for example the treatment of heartfailure, myocardial infarction, cardiac hypertrophy, diabeticnephropathy, diabetic cardiomyopathy, cardiac fibrosis, or ischemiaand/or reperfusion damage, or for cardioprotection, wherein thetreatment of diseases comprises their therapy and prophylaxis asmentioned above, as well as their use for the manufacture of amedicament for the inhibition of cathepsin A. A subject of the inventionalso are methods for the treatment of the diseases mentioned above orbelow, including the treatment of any one of the mentioned diseases, forexample the treatment of heart failure, myocardial infarction, cardiachypertrophy, diabetic nephropathy, diabetic cardiomyopathy, cardiacfibrosis, or ischemia and/or reperfusion damage, or forcardioprotection, which comprise administering an efficacious amount ofat least one compound of the formula I and/or a physiologicallyacceptable salt thereof and/or solvate thereof to a human or an animalwhich is in need thereof. The compounds of the formula I andpharmaceutical compositions and medicaments comprising them can beadministered enterally, for example by oral, sublingual or rectaladministration, parenterally, for example by intravenous, intramuscular,subcutaneous or intraperitoneal injection or infusion, or by anothertype of administration such as topical, percutaneous, transdermal,intra-articular or intraocular administration.

The compounds of the formula I and their physiologically acceptablesalts and solvates can also be used in combination with otherpharmaceutical active compounds, wherein in such a combination use thecompounds of the formula I and/or their physiologically acceptable saltsand/or solvates and one or more other pharmaceutical active compoundscan be present in one and the same pharmaceutical composition or in twoor more pharmaceutical compositions for separate, simultaneous orsequential administration. Examples of such other pharmaceutical activecompounds are diuretics, aquatics, angiotensin converting enzyme (ACE)inhibitors, angiotensin receptor blockers, renin inhibitors, betablockers, digoxin, aldosterone antagonists, NO donors, nitrates,hydralazines, ionotropes, vasopressin receptor antagonists, solubleguanylate cyclase activators, statins, peroxisome proliferator-activatedreceptor-alpha (PPAR-α) activators, peroxisome proliferator-activatedreceptor-gamma (PPAR-γ) activators, rosiglitazone, pioglitazone,metformin, sulfonylureas, glucagon-like peptide 1 (GLP-1) agonists,dipeptidyl peptidase IV (DPPIV) inhibitors, insulins, anti-Arrhythmics,endothelin receptor antagonists, calcium antagonists, phosphodiesteraseinhibitors, phosphodiesterase type 5 (PDE5) inhibitors, factor II/factorIIa inhibitors, factor IX/factor IXa inhibitors, factor X/factor Xainhibitors, factor XIII/factor XIIIa inhibitors, heparins, glycoproteinIIb/IIIa antagonists, P2Y12 receptor antagonists, clopidogrel,coumarins, cyclooxygenase inhibitors, acetylsalicylic acid, RAF kinaseinhibitors and p38 mitogen-activated protein kinase inhibitors. Asubject of the present invention also is the said combination use of anyone or more of the compounds of the formula I disclosed herein and theirphysiologically acceptable salts and solvates, with any one or more, forexample one or two, of the mentioned other pharmaceutical activecompounds.

The pharmaceutical compositions and medicaments according to theinvention normally contain from about 0.5 to about 90 percent by weightof compounds of the formula I and/or physiologically acceptable saltsand/or solvates thereof, and an amount of active ingredient of theformula I and/or its physiologically acceptable salt and/or solvatewhich in general is from about 0.2 mg to about 1.5 g, particularly fromabout 0.2 mg to about 1 g, more particularly from about 0.5 mg to about0.5 g, for example from about 1 mg to about 0.3 g, per unit dose.Depending on the kind of the pharmaceutical composition and otherparticulars of the specific case, the amount may deviate from theindicated ones. The production of the pharmaceutical compositions andmedicaments can be carried out in a manner known per se. For this, thecompounds of the formula I and/or their physiologically acceptable saltsand/or solvates are mixed together with one or more solid or liquidvehicles and/or excipients, if desired also in combination with one ormore other pharmaceutical active compounds such as those mentionedabove, and brought into a suitable form for dosage and administration,which can then be used in human medicine or veterinary medicine.

As vehicles, which may also be looked upon as diluents or bulkingagents, and excipients suitable organic and inorganic substances can beused which do not react in an undesired manner with the compounds of theformula I. As examples of types of excipients, or additives, which canbe contained in the pharmaceutical compositions and medicaments,lubricants, preservatives, thickeners, stabilizers, disintegrants,wetting agents, agents for achieving a depot effect, emulsifiers, salts,for example for influencing the osmotic pressure, buffer substances,colorants, flavorings and aromatic substances may be mentioned. Examplesof vehicles and excipients are water, vegetable oils, waxes, alcoholssuch as ethanol, isopropanol, 1,2-propanediol, benzyl alcohols,glycerol, polyols, polyethylene glycols or polypropylene glycols,glycerol triacetate, polyvinylpyrrolidone, gelatin, cellulose,carbohydrates such as lactose or starch like corn starch, sodiumchloride, stearic acid and its salts such as magnesium stearate, talc,lanolin, petroleum jelly, or mixtures thereof, for example saline ormixtures of water with one or more organic solvents such as mixtures ofwater with alcohols. For oral and rectal use, pharmaceutical forms suchas, for example, tablets, film-coated tablets, sugar-coated tablets,granules, hard and soft gelatin capsules, suppositories, solutions,including oily, alcoholic or aqueous solutions, syrups, juices or drops,furthermore suspensions or emulsions, can be used. For parenteral use,for example by injection or infusion, pharmaceutical forms such assolutions, for example aqueous solutions, can be used. For topical use,pharmaceutical forms such as ointments, creams, pastes, lotions, gels,sprays, foams, aerosols, solutions or powders can be used. Furthersuitable pharmaceutical forms are, for example, implants and patches andforms adapted to inhalation. The compounds of the formula I and theirphysiologically acceptable salts can also be lyophilized and theobtained lyophilizates used, for example, for the production ofinjectable compositions. In particular for topical application, alsoliposomal compositions are suitable. The pharmaceutical compositions andmedicaments can also contain one or more other active ingredientsand/or, for example, one or more vitamins.

As usual, the dosage of the compounds of the formula I depends on thecircumstances of the specific case and is adjusted by the physicianaccording to the customary rules and procedures. It depends, forexample, on the compound of the formula I administered and its potencyand duration of action, on the nature and severity of the individualsyndrome, on the sex, age, weight and the individual responsiveness ofthe human or animal to be treated, on whether the treatment is acute orchronic or prophylactic, or on whether further pharmaceutical activecompounds are administered in addition to a compound of the formula I.Normally, in the case of administration to an adult weighing about 75kg, a dose from about 0.1 mg to about 100 mg per kg per day, inparticular from about 1 mg to about 20 mg per kg per day, for examplefrom about 1 mg to about 10 mg per kg per day (in each case in mg per kgof body weight), is administered. The daily dose can be administered inthe form of a single dose or divided into a number of individual doses,for example two, three or four individual doses. The administration canalso be carried out continuously, for example by continuous injection orinfusion. Depending on the individual behavior in a specific case, itmay be necessary to deviate upward or downward from the indicateddosages.

Besides as a pharmaceutical active compound in human medicine andveterinary medicine, the compounds of the formula I can also be employedas an aid in biochemical investigations or as a scientific tool or fordiagnostic purposes, for example in in-vitro diagnoses of biologicalsamples, if an inhibition of cathepsin A is intended. The compounds ofthe formula I and their salts can also be used as intermediates, forexample for the preparation of further pharmaceutical active substances.

The following examples illustrate the invention.

Abbreviations

-   ACN acetonitrile-   DCM dichloromethane-   DMF N,N-dimethylformamide-   DMSO dimethyl sulfoxide-   EA ethyl acetate-   EDIA N-ethyl-diisopropylamine-   FA formic acid-   MOH methanol-   NEM N-ethyl-morpholine-   TFA trifluoroacetic acid-   THF tetrahydrofuran-   TOTU    O-(cyano(ethoxycarbonyl)methyleneamino)-N,N,N′,N′-tetramethyluronium    tetrafluoroborate

When example compounds containing a basic group were purified bypreparative high pressure liquid chromatography (HPLC) on reversed phase(RP) column material and, as customary, the eluent was a gradientmixture of water and acetonitrile containing trifluoroacetic acid, theywere in part obtained in the form of their acid addition salts withtrifluoroacetic acid, depending on the details of the work-up such asevaporation or lyophilization conditions. In the names of the examplecompounds and the structural formulae such contained trifluoroaceticacid is not specified. Likewise are other acid components of examplecompounds obtained in the form of an acid addition salt in general notspecified in the name and the formula.

The prepared compounds were in general characterized by spectroscopicdata and chromatographic data, in particular mass spectra (MS) and HPLCretention times (Rt; in min) which were obtained by combined analyticalHPLC/MS characterization (LC/MS), and/or nuclear magnetic resonance(NMR) spectra. Unless specified otherwise, ¹H-NMR spectra were recordedat 500 MHz in D₆-DMSO as solvent at 298 K. In the NMR characterization,the chemical shift δ (in ppm), the number of hydrogen atoms (H), and themultiplicity (s: singlet, d: doublet, dd: doublet of doublets, t:triplet, q: quartet, m: multiplet) of the peaks as determined from thegraphically depicted spectra are given. In the MS characterization, ingeneral the mass number (m/z) of the peak of the molecular ion [M], forexample [M⁺], or of a related ion such as the ion [M+1], for example[(M+1)⁺], i.e. the protonated molecular ion [(M+H)⁺], or the ion [M−1],for example [(M−1)⁻], i.e. the deprotonated molecular ion [(M−H)⁻],which was formed depending on the ionization method used, is given.Generally, the ionization method was electrospray ionization (ES). Theparticulars of the LC/MS methods used are as follows.

Method LC1

Column: YMC-Pack Jsphere H80, 33×2.1 mm, 4 μm; flow: 1.3 ml/min; roomtemperature; eluent A: water+0.05% FA; eluent B: ACN+0.05% FA; gradient:from 95% A+5% B to 5% A+95% B within 2.5 min; MS ionization method: ES⁺

Method LC2

Column: Waters XBridge C18, 50×4.6 mm, 2.5 μm; flow: 1.3 ml/min; roomtemperature; eluent A: water+0.1% FA; eluent B: ACN+0.08% FA; gradient:from 97% A+3% B to 40% A+60% B within 3.5 min, then to 2% A+98% B within0.5 min, then 2% A+98% B for 1.0 min, then to 97% A+3% B within 0.2 min,then 97% A+3% B for 1.3 min; MS ionization method: ES⁻

Method LC3

Column: YMC-Pack Jsphere H80, 33×2.1 mm, 4 μm; flow: 1.0 ml/min; roomtemperature; eluent A: water+0.05% TFA; eluent B: ACN+0.05% TFA;gradient: 98% A+2% B for 1.0 min, then to 5% A+95% B within 4.0 min,then 5% A+95% B for 1.25 min; MS ionization method: ES⁺

Method LC4

Column: Waters XBridge C18, 50×4.6 mm, 2.5 μm; flow: 1.3 ml/min; 40° C.;eluent A: water+0.1% FA; eluent B: ACN+0.1% FA; gradient: from 97% A+3%B to 40% A+60% B within 3.5 min, then to 2% A+98% B within 0.5 min, then2% A+98% B for 1.0 min, then to 97% A+3% B within 0.2 min, then 97% A+3%B for 1.3 min; MS ionization method: ES⁻

Method LC5

Column: Waters XBridge C18, 50×4.6 mm, 2.5 μm; flow: 1.7 ml/min; 40° C.;eluent A: water+0.05% FA; eluent B: ACN+0.05% TFA; gradient: from 95%A+5% B to 5% A+95% B within 3.3 min, then 5% A+95% B for 0.55 min, thento 95% A+5% B within 0.15 min; MS ionization method: ES⁺

Method LC6

Column: Waters XBridge C18, 50×4.6 mm, 2.5 μm; flow: 1.7 ml/min; 50° C.;eluent A: water+0.05% TFA; eluent B: ACN+0.05% TFA; gradient: 95% A+5% Bfor 0.2 min, then to 5% A+95% B within 2.2 min, then 5% A+95% B for 1.1min, then to 95% A+5% B within 0.1 min, then 95% A+5% B for 0.9 min; MSionization method: ES⁺

Method LC7

Column: Waters XBridge C18, 50×4.6 mm, 2.5 μm; flow: 1.7 ml/min; 40° C.;eluent A: water+0.05% TFA; eluent B: ACN+0.05% TFA; gradient: 95% A+5% Bfor 0.2 min, then to 5% A+95% B within 2.2 min, then 5% A+95% B for 0.8min, then to 95% A+5% B within 0.1 min, then 95% A+5% B for 0.7 min; MSionization method: ES⁺

Method LC8

Column: Waters XBridge C18, 50×4.6 mm, 2.5 μm; flow: 1.7 ml/min; 40° C.;eluent A: water+0.05% TFA; eluent B: ACN+0.05% TFA; gradient: 95% A+5% Bfor 0.3 min, then to 5% A+95% B within 3.2 min, then 5% A+95% B for 0.5min; MS ionization method: ES⁺

Method LC9

Column: Merck Chromolith FastGrad RP-18e, 50×2 mm; flow: 2.0 ml/min;room temperature; eluent A: water+0.05% TFA; eluent B: ACN+0.05% TFA;gradient: 98% A+2% B for 0.2 min, then to 2% A+98% B within 2.2 min,then 2% A+98% B for 0.8 min, then to 98% A+2% B within 0.1 min, then 98%A+2% B for 0.7 min; MS ionization method: ES⁺

Method LC10

Column: Waters XBridge C18, 50×4.6 mm, 2.5 μm; flow: 1.3 ml/min; 45° C.;eluent A: water+0.1% FA; eluent B: ACN+0.1% FA; gradient: from 97% A+3%B to 40% A+60% B within 3.5 min, then to 2% A+98% B within 0.5 min, then2% A+98% B for 1.0 min, then to 97% A+3% B within 0.2 min, then 97% A+3%B for 1.3 min; MS ionization method: ES⁺

Method LC11

Column: Waters HPLC BEH C18, 50×2.1 mm, 1.7 μm; flow: 0.9 ml/min; 55°C.; eluent A: water+0.1% FA; eluent B: ACN+0.08% FA; gradient: from 95%A+5% B to 5% A+95% B within 1.1 min, then 5% A+95% B for 0.6 min, thento 95% A+5% B within 0.1 min, then 95% A+5% B for 0.2 min; MS ionizationmethod: ES⁺

Method LC12

Column: YMC-Pack Jsphere H80, 33×2.1 mm, 4 μm; flow: 1.0 ml/min; roomtemperature; eluent A: water+0.05% TFA; eluent B: MOH+0.05% TFA;gradient: 98% A+2% B for 1.0 min, then to 5% A+95% B within 4.0 min,then 5% A+95% B for 1.25 min; MS ionization method: ES⁺

Method LC13.

Column: Waters XBridge C18, 50×4.6, 2.5 μm; flow: 1.3 ml/min; roomtemperature; eluent A: water+0.1% FA; eluent B: ACN+0.08% FA; gradient:from 97% A+3% B to 2% A+98% B within 18.0 min, then 2% A+98% B for 1.0min, then to 97% A+3% B within 0.5 min, then 97% A+3% B for 0.5 min; MSionization method: ES⁺

Method LC14

Column: Waters XBridge C18 4.6*50 mm; 2.5 um, flow: 1.3 ml/min; eluent AH₂O+0.1% FA; eluent B: ACN+0.08% FA; gradient: from 97% A+3% B to 2%A+98% B within 18 min, then 2% A+98% B for 1 min, then to 97% A+3% Bwithin 0.5 min then to 97:3 for 0.5 min.

SYNTHESIS EXAMPLE 11-(2-Fluoro-phenyl)-5-hydroxy-1H-pyrazole-3-carboxylic acid

Sulfuric acid (400 ml) was added slowly to water (400 ml). After coolingto 5° C., 2-fluoro-phenylhydrazine hydrochloride (123 g, 757 mmol) wasadded resulting in a brown suspension. Then a solution of oxalaceticacid (100 g, 757 mmol) in water (400 ml) was added slowly during aperiod of 25 min. After 2 h the conversion was complete and the solidwas filtered. After washing with water the solid was dried. The productwas obtained as light brown solid (151 g, 90%).

Analogously as described in synthesis example 1, the following compoundswere prepared:

-   5-hydroxy-1-phenyl-1H-pyrazole-3-carboxylic acid-   1-(2-fluoro-phenyl)-5-hydroxy-1H-pyrazole-3-carboxylic acid-   1-(2,5-dimethyl-phenyl)-5-hydroxy-1H-pyrazole-3-carboxylic acid-   1-(3,5-dimethyl-phenyl)-5-hydroxy-1H-pyrazole-3-carboxylic acid-   1-(2-chloro-phenyl)-5-hydroxy-1H-pyrazole-3-carboxylic acid-   1-(3-chloro-phenyl)-5-hydroxy-1H-pyrazole-3-carboxylic acid-   1-(4-chloro-phenyl)-5-hydroxy-1H-pyrazole-3-carboxylic acid-   1-(3-chloro-4-fluoro-phenyl)-5-hydroxy-1H-pyrazole-3-carboxylic acid-   5-hydroxy-1-(3-methoxy-phenyl)-1H-pyrazole-3-carboxylic acid-   1-(2-chloro-pyridin-4-yl)-5-hydroxy-1H-pyrazole-3-carboxylic acid-   1-(5-chloro-pyridin-2-yl)-5-hydroxy-1H-pyrazole-3-carboxylic acid-   5-hydroxy-1-(4-trifluoromethyl-pyrimidin-2-yl)-1H-pyrazole-3-carboxylic    acid-   5-hydroxy-1-(pyridin-4-yl)-1H-pyrazole-3-carboxylic acid-   5-hydroxy-1-(pyridin-3-yl)-1H-pyrazole-3-carboxylic acid-   5-hydroxy-1-(2-trifluoromethyl-phenyl)-1H-pyrazole-3-carboxylic acid-   5-hydroxy-1-(3,5-difluoro-phenyl)-1H-pyrazole-3-carboxylic acid-   5-hydroxy-1-(2,5-difluoro-phenyl)-1H-pyrazole-3-carboxylic acid-   5-hydroxy-1-(2,6-difluoro-phenyl)-1H-pyrazole-3-carboxylic acid-   1-(3-chloro-2-fluoro-phenyl)-5-hydroxy-1H-pyrazole-3-carboxylic acid-   1-cyclopentyl-5-hydroxy-1H-pyrazole-3-carboxylic acid-   1-cyclohexyl-5-hydroxy-1H-pyrazole-3-carboxylic acid-   5-hydroxy-1-(3-sulfamoyl-phenyl)-1H-pyrazole-3-carboxylic acid-   5-hydroxy-1-(2-methanesulfonyl-phenyl)-1H-pyrazole-3-carboxylic acid-   1-tert-butyl-5-hydroxy-1H-pyrazole-3-carboxylic acid

SYNTHESIS EXAMPLE 2(S)-3-{[1-(2-Fluoro-phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]-amino}-3-o-tolyl-propionicacid

0.45 mmol of 1-(2-fluoro-phenyl)-5-hydroxy-1H-pyrazole-3-carboxylic acidwere dissolved in 5 ml of DMF, 0.54 mmol of TOTU and 1.125 mmol of NEMwere added, and the mixture was stirred for 5 min at room temperature.Then 0.495 mmol of (S)-3-amino-3-o-tolyl-propionic acid were added andthe mixture stirred overnight at room temperature. The solvent wasevaporated in vacuo and the residue subjected to preparative HPLC togive the title compound in a yield of 28%.

SYNTHESIS EXAMPLE 3 5-Methoxy-1-phenyl-1H-pyrazole-3-carboxylic acid

600 mg (2.94 mmol) of 5-hydroxy-1-phenyl-1H-pyrazole-3-carboxylic acidwere dissolved in 30 ml of DMF, 1.92 (5.9 mmol) of cesium carbonate and1.04 g (7.35 mmol) of iodomethane were added, and the resulting mixturewas heated for 4 h to 80° C. The mixture was filtrated and the solventremoved in vacuo. The residue was dissolved in 20 ml of MOH and 5.9 mlof an aqueous 1 M solution of sodium hydroxide. After stirring overnightthe reaction was complete. The solvent was removed and the residuesubjected to preparative HPLC to give the title compound in a yield of38%.

Analogously as described in synthesis example 3, the following compoundswere prepared:

-   1-(2-fluoro-phenyl)-5-methoxy-1H-pyrazole-3-carboxylic acid-   1-(2-chloro-phenyl)-5-methoxy-1H-pyrazole-3-carboxylic acid-   1-(3-fluoro-phenyl)-5-methoxy-1H-pyrazole-3-carboxylic acid-   1-(2,5-difluoro-phenyl)-5-methoxy-1H-pyrazole-3-carboxylic acid-   1-tert-butyl-5-methoxy-1H-pyrazole-3-carboxylic acid

SYNTHESIS EXAMPLE 4 Methyl1-(2-fluoro-phenyl)-5-hydroxy-1H-pyrazole-3-carboxylate

1 g (4.5 mmol) of 1-(2-fluoro-phenyl)-5-hydroxy-1H-pyrazole-3-carboxylicacid was dissolved in 20 ml of MOH. 535 mg (4.5 mmol) of thionylchloride was added with caution and the mixture is stirred for 4 h atroom temperature. Then the solvent was removed in vacuo to give 900 mg(85%) of the crude title compound which was used in the following stepwithout further purification.

SYNTHESIS EXAMPLE 5 Methyl1-(2-fluoro-phenyl)-5-hydroxy-1H-pyrazole-3-carboxylate

Dimethyl acetylenedicarboxylate (87.4 g, 757 mmol) was added to asolution of 2-fluoro-phenylhydrazine hydrochloride (100 g, 615 mmol) inmethanol (1 l) at 0° C. Then triethylamine (125 g, 1.23 mol) was addedslowly during 60 min. The solution was stirred for 16 h at roomtemperature, the solvent then removed under reduced pressure and theresidue dissolved in EA (500 ml). After washing with aqueoushydrochloric acid (500 ml), the solvent was removed under reducedpressure. The title compound was obtained as an almost white solid inquantitative yield.

SYNTHESIS EXAMPLE 65-Cyclopropylmethoxy-1-(2-fluoro-phenyl)-1H-pyrazole-3-carboxylic acid

Step 1:5-Cyclopropylmethoxy-1-(2-fluoro-phenyl)-1H-pyrazole-3-carboxylic acidmethyl ester

150 mg (0.635 mmol) of methyl1-(2-fluoro-phenyl)-5-hydroxy-1H-pyrazole-3-carboxylate were dissolvedin 8 ml of THF. 207 mg (0.635 mmol) of cesium carbonate and 400 mg (2.96mmol) of bromomethyl-cyclopropane were added and the mixture was heatedto 50° C. for 6 h. Then the mixture was filtrated and the solventremoved in vacuo. The crude title compound was used in the next stepwithout further purification.

Step 2:5-Cyclopropylmethoxy-1-(2-fluoro-phenyl)-1H-pyrazole-3-carboxylic acid

The crude compound obtained in step 1 was dissolved in 10 ml ofmethanol. 1.4 ml of an aqueous 1 M solution of sodium hydroxide wereadded and the mixture was stirred overnight at room temperature. Thesolvent was removed in vacuo and the residue purified by preparativeHPLC to give 102 mg (58%) of the title compound

Analogously as described in synthesis example 6, the following compoundswere prepared:

-   5-cyclopropylmethoxy-1-phenyl-1H-pyrazole-3-carboxylic acid-   5-cyclopropylmethoxy-1-(2,6-difluoro-phenyl)-1H-pyrazole-3-carboxylic    acid-   5-dimethylcarbamoyl-methoxy-1-(2-fluoro-phenyl)-1H-pyrazole-3-carboxylic    acid    (using 2 equivalents of 2-chloro-N,N-dimethyl-acetamide instead of    bromomethyl-cyclopropane in step 1)-   1-(2-fluoro-phenyl)-5-(2-oxo-2-pyrrolidin-1-yl-ethoxy)-1H-pyrazole-3-carboxylic    acid    (using 2 equivalents of 2-chloro-1-pyrrolidin-1-yl-ethanone instead    of bromomethyl-cyclopropane in step 1)

SYNTHESIS EXAMPLE 71-(2-Fluoro-phenyl)-5-methoxy-1H-pyrazole-3-carboxylic acid

Step 1: Methyl 1-(2-fluoro-phenyl)-5-methoxy-1H-pyrazole-3-carboxylate

Potassium carbonate (27.8 g, 201 mmol) and water (3.62 g, 201 mmol) wereadded to a suspension of methyl1-(2-fluoro-phenyl)-5-hydroxy-1H-pyrazole-3-carboxylate (31.6 g, 134mmol) in methyl isobutyl ketone (323 ml) at room temperature. Thendimethyl sulfate (16.9 g, 134 mmol) was added slowly and the mixture wasstirred for 2.5 h. Water was added and the phases were separated. Theorganic phase was evaporated to give 27.4 g of the title compound as awhite solid.

Step 2: 1-(2-Fluoro-phenyl)-5-methoxy-1H-pyrazole-3-carboxylic acid

109 ml of an aqueous 2 M solution of sodium hydroxide (218 mmol) wereadded to a solution of the crude methyl ester obtained in step 1 inmethyl isobutyl ketone. After 16 h at room temperature the conversionwas complete and the phases were separated.

The aqueous phase was acidified to pH 3 with hydrochloric acid andextracted with EA. The organic phases were evaporated to give 18.9 g(59% over two steps) of the title compound.

Analogously as described in synthesis example 7, the following compoundswere prepared, using diethyl sulfate instead of dimethyl sulfate in step1:

-   5-ethoxy-1-(2-fluoro-phenyl)-1H-pyrazole-3-carboxylic acid-   5-ethoxy-1-(2-chloro-phenyl)-1H-pyrazole-3-carboxylic acid-   5-ethoxy-1-phenyl-1H-pyrazole-3-carboxylic acid

SYNTHESIS EXAMPLE 8 Ethyl (S)-3-amino-3-(2-methyl-phenyl)-propionate

(S)-3-Amino-3-(2-methyl-phenyl)propionic acid (10.0 g, 55.8 mmol) wassuspended in 2-methyltetrahydrofuran (100 ml) and ethanol (25.7 g, 558mmol) was added. The mixture was heated to 80° C. and thionyl chloride(6.64 g, 55.8 mmol) was added slowly. After 2 h at 80° C. the solventswere almost completely removed by distillation. After cooling themixture was stirred at room temperature for 16 h. Then more solvent wasremoved under reduced pressure to give the title compound in the form ofethyl (S)-3-amino-3-(2-methyl-phenyl)-propionate hydrochloride togetherwith some 2-methyltetrahydrofuran in quantitative yield.

SYNTHESIS EXAMPLE 9 Ethyl(S)-3-{[1-(2-fluoro-phenyl)-5-methoxy-1H-pyrazole-3-carbonyl]-amino}-3-(2-methyl-phenyl)-propionate

Step 1: 1-(2-Fluoro-phenyl)-5-methoxy-1H-pyrazole-3-carbonyl chloride

A suspension of 1-(2-fluoro-phenyl)-5-methoxy-1H-pyrazole-3-carboxylicacid (39.1 g, 167 mmol) in 2-methyltetrahydrofuran (300 ml) was cooledto 0° C. and DMF (293 μl, 3.81 mmol) was added. Oxalyl chloride (23.1 g,182 mmol) was added dropwise. After 16 h at room temperature ca. 100 mlof the solvent were removed by distillation. The resulting suspension ofthe title compound was used directly in the next step.

Step 2: Ethyl(S)-3-{[1-(2-fluoro-phenyl)-5-methoxy-1H-pyrazole-3-carbonyl]-amino}-3-(2-methyl-phenyl)-propionate

A solution of ethyl (S)-3-amino-3-(2-methyl-phenyl)-propionatehydrochloride (42.4 g, 174 mmol) in 2-methyltetrahydrofuran (200 ml) wasadded to the suspension of1-(2-fluoro-phenyl)-5-methoxy-1H-pyrazole-3-carbonyl chloride in ca. 200ml of 2-methyltetrahydrofuran obtained in step 1. Triethylamine (33.5 g,331 mmol) was added dropwise under ice cooling. After the completeaddition of the triethylamine the conversion was complete and water wasadded. The phases were separated and the organic phase was washed withwater and evaporated. The residue was dissolved in2-methyltetrahydrofuran (500 ml) and washed with 1 M hydrochloric acid.The organic phase was dried and the solvent was removed under reducedpressure to give 70.4 g (99% over two step) of the title compound as alight brown oil.

SYNTHESIS EXAMPLE 10(S)-3-{[1-(2-Fluoro-phenyl)-5-methoxy-1H-pyrazole-3-carbonyl]-amino}-3-(2-methyl-phenyl)-propionicacid

82.8 ml of an aqueous 4 M solution of sodium hydroxide (331 mmol) wereadded to a solution of ethyl(S)-3-{[1-(2-fluoro-phenyl)-5-methoxy-1H-pyrazole-3-carbonyl]-amino}-3-(2-methyl-phenyl)-propionate(70.4 g, 165 mmol) in 2-methyltetrahydrofuran (500 ml) at roomtemperature. The mixture was stirred at room temperature for 2 h, thenat 40° C. for 2 h and then at room temperature for 16 h. The phases wereseparated and the aqueous phase acidified to pH 3 with hydrochloricacid. The product partially precipitated upon acidification. The aqueousfiltrate was extracted with EA. The extracts were evaporated and theresidue was washed with isopropyl acetate. The two batches were combinedto give 53.6 g (82%) of the title compound as a white crystallinepowder.

SYNTHESIS EXAMPLE 115-(2-Cyano-benzyloxy)-1-(2-fluoro-phenyl)-1H-pyrazole-3-carboxylic acid

1-(2-Fluoro-phenyl)-5-hydroxy-1H-pyrazole-3-carboxylic acid methyl ester(200 mg, 0.847 mmol) were dissolved in 5 ml of DMF and cesium carbonate(552 mg, 1.7 mmol) and 2-bromomethyl-benzonitrile (166 mg, 0.85 mmol)were added. The mixture was stirred for 5 h at 60° C., filtrated and thesolvent was removed in vacuo. The obtained residue of crude5-(2-cyano-benzyloxy)-1-(2-fluoro-phenyl)-1H-pyrazole-3-carboxylic acidmethyl ester (235 mg, 79%) was dissolved in a mixture of THF, MOH andwater (3 ml each), lithium hydroxide (64.1 mg, 2.7 mmol) was added, andthe mixture was stirred overnight at room temperature. After evaporationof the solvent the residue was subjected to column chromatography(silica gel, DCM/MOH 9:1) to give 195 mg (86%) of the title compound.

SYNTHESIS EXAMPLE 12(S)-3-{[5-(2-Cyano-benzyloxy)-1-(2-fluoro-phenyl)-1H-pyrazole-3-carbonyl]-amino}-3-O—tolyl-propionic acid ethyl ester

190 mg (0.56 mmol) of(2-cyano-benzyloxy)-1-(2-fluoro-phenyl)-1H-pyrazole-3-carboxylic acidwere dissolved in 6 ml of DMF, and 213.5 mg (0.56 mmol) ofO-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluroniumhexafluorophosphate and 145.5 mg (1.12 mmol) of NEM were added. Then116.7 mg (0.56 mmol) of ethyl (S)-3-amino-3-(2-methyl-phenyl)-propionatewere added and the mixture was stirred for 3 h at room temperature. Thesolvent was removed in vacuo and the residue subjected to columnchromatography (silica gel, DCM/MOH 100:1) to give 210 mg (71%) of thetitle compound.

SYNTHESIS EXAMPLE 13(S)-3-{[5-(2-Cyano-benzyloxy)-1-(2-fluoro-phenyl)-1H-pyrazole-3-carbonyl]-amino}-3-o-tolyl-propionicacid

210 mg (0.4 mmol) of(S)-3-{[5-(2-cyano-benzyloxy)-1-(2-fluoro-phenyl)-1H-pyrazole-3-carbonyl]-amino}-3-o-tolyl-propionicacid ethyl ester were dissolved in a mixture of THF, MOH and water (2 mleach), lithium hydroxide (28.7 mg, 1.2 mmol) was added, and the mixturewas stirred for 3 h at room temperature. After evaporation of thesolvent the residue was subjected to aqueous work-up using EA and a 10%aqueous solution of citric acid. After evaporation of the organic phasethe residue was subjected to column chromatography (silica gel, DCM/MOH10:1) to give 45 mg (23%) of the title compound.

SYNTHESIS EXAMPLE 14(S)-3-{[1-(2-Fluoro-phenyl)-5-(3-methyl-oxetan-3-ylmethoxy)-1H-pyrazole-3-carbonyl]-amino}-3-(2-methyl-phenyl)-propionicacid ethyl ester

101 mg (0.245 mmol) of(S)-3-{[1-(2-fluoro-phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]-amino}-3-(2-methyl-phenyl)-propionicacid ethyl ester (prepared from1-(2-fluoro-phenyl)-5-hydroxy-1H-pyrazole-3-carboxylic acid and ethyl(S)-3-amino-3-(2-methyl-phenyl)-propionate analogously as described insynthesis example 2) were dissolved in 3 ml of DMF, and 160 mg (0.5mmol) of cesium carbonate and 41.3 mg (0.245 mmol) of3-bromomethyl-3-methyl-oxetane were added. The mixture was stirred for 4h at 65° C. After evaporation of the solvent the residue was subjectedto an aqueous work-up with EA and 10% aqueous solution of citric acid.After removal of the solvent from the organic phase 100 mg (82%) of theproduct are obtained.

SYNTHESIS EXAMPLE 15(S)-3-{[1-(2-Fluoro-phenyl)-5-(3-methyl-oxetan-3-ylmethoxy)-1H-pyrazole-3-carbonyl]-amino}-3-(2-methyl-phenyl)-propionicacid

100 mg (0.2 mmol) of(S)-3-{[1-(2-fluoro-phenyl)-5-(3-methyl-oxetan-3-ylmethoxy)-1H-pyrazole-3-carbonyl]-amino}-3-(2-methyl-phenyl)-propionicacid ethyl ester were dissolved in a mixture of THF, MOH and water (2 mleach), and 14.5 mg (0.61 mmol) of lithium hydroxide were added. Themixture was stirred overnight at room temperature and the solventremoved. The residue was subjected to column chromatography (silica gel,DCM/MOH 9:1) to give 75 mg (75%) of the title compound.

SYNTHESIS EXAMPLE 16 Pyrrolidine-1-carboxylic acid5-((S)-2-carboxy-1-o-tolyl-ethylcarbamoyl)-2-(2-fluoro-phenyl)-2H-pyrazol-3-ylester

Step 1:1-(2-Fluoro-phenyl)-5-(pyrrolidine-1-carbonyloxy)-1H-pyrazole-3-carboxylicacid

150 mg (0.675 mmol) of1-(2-fluoro-phenyl)-5-hydroxy-1H-pyrazole-3-carboxylic acid weredissolved in 5 ml of THF. 440 mg (1.35 mmol) of cesium carbonate and90.2 mg (0.675 mmol) of pyrrolidine-1-carbonyl chloride were added andthe mixture was heated to 50° C. for 4 h. Then the mixture was filtratedand the filtrate containing the title compound directly used in the nextstep.

Step 2: Pyrrolidine-1-carboxylic acid5-((S)-2-carboxy-1-o-tolyl-ethylcarbamoyl)-2-(2-fluoro-phenyl)-2H-pyrazol-3-ylester

0.675 mmol of TOTU and 1.35 mmol of EDIA were added to the filtratecontaining1-(2-fluoro-phenyl)-5-(pyrrolidine-1-carbonyloxy)-1H-pyrazole-3-carboxylicacid obtained in step 1. The mixture was stirred for 5 min at roomtemperature, and then 0.675 mmol of(S)-3-amino-3-(2-methyl-phenyl)-propionic acid were added and themixture was stirred overnight at RT. Then the solvent was evaporated andthe residue subjected to preparative HPLC to give the title compound ina yield of 67%.

Analogously as described in synthesis example 16, step 1, the followingcompounds were prepared:

-   5-dimethylcarbamoyloxy-1-(2-fluoro-phenyl)-1H-pyrazole-3-carboxylic    acid-   1-(2-fluoro-phenyl)-5-(piperidine-1-carbonyloxy)-1H-pyrazole-3-carboxylic    acid-   1-(2-fluoro-phenyl)-5-(methyl-phenyl-carbamoyloxy)-1H-pyrazole-3-carboxylic    acid

SYNTHESIS EXAMPLE 174-Bromo-1-(2-fluoro-phenyl)-5-methoxy-1H-pyrazole-3-carboxylic acid

50 mg (0.21 mmol) of1-(2-fluoro-phenyl)-5-methoxy-1H-pyrazole-3-carboxylic acid weredissolved in 1.5 ml of acetic acid, sodium acetate (35 mg, 0.42 mmol)and bromine (50 mg, 0.21 mmol) were added and the mixture was stirredfor 60 min. The solvent was removed in vacuo and the residue subjectedto an aqueous work-up. The obtained crude title compound (60 mg) wasused in the next step without further purification.

SYNTHESIS EXAMPLE 184-Chloro-1-(2-fluoro-phenyl)-5-methoxy-1H-pyrazole-3-carboxylic acid

Step 1: 4-Chloro-1-(2-fluoro-phenyl)-5-methoxy-1H-pyrazole-3-carboxylicacid methyl ester

300 mg (1.2 mmol) of1-(2-fluoro-phenyl)-5-methoxy-1H-pyrazole-3-carboxylic acid methyl esterwas dissolved in 3 ml of acetic acid. 162 mg (1.2 mmol) of sulfurylchloride were added and the mixture stirred for 4 h at room temperature.The solvent was removed in vacuo and the residue subjected to acidicaqueous work-up. The obtained crude title compound (330 mg) was used inthe hydrolysis step without further purification.

Step 2: 4-Chloro-1-(2-fluoro-phenyl)-5-methoxy-1H-pyrazole-3-carboxylicacid

The crude4-chloro-1-(2-fluoro-phenyl)-5-methoxy-1H-pyrazole-3-carboxylic acidmethyl ester obtained (330 mg, 1.16 mmol) obtained in step 1 wasdissolved in 6 ml of dioxane and 5.8 ml of an aqueous 1 M solution oflithium hydroxide were added. The mixture was stirred for 30 min at 56°C. Acidic aqueous work-up gave 320 mg (100%) of the title compound.

SYNTHESIS EXAMPLE 194-Fluoro-1-(2-fluoro-phenyl)-5-methoxy-1H-pyrazole-3-carboxylic acid

Step 1: 4-Fluoro-1-(2-fluoro-phenyl)-5-methoxy-1H-pyrazole-3-carboxylicacid methyl ester

200 mg (0.8 mmol) of1-(2-fluoro-phenyl)-5-methoxy-1H-pyrazole-3-carboxylic acid methyl esterwere dissolved in 2 ml of acetonitrile and 745 mg (1.99 mmol) of1-chloro-methyl-4-fluoro-1,4-diazoniabicyclo[2.2.2]octanebis(tetrafluoroborate) (Selectfluor®) were added. The mixture wasstirred overnight. Then, irrespective of the incomplete reaction,diethyl ether, water and 2 N hydrochloric acid were added, the organicphase was separated, the solvent evaporated and the residue subjected topreparative HPLC. 70 mg (33%) of the title compound were obtained.

Step 2: 4-Fluoro-1-(2-fluoro-phenyl)-5-methoxy-1H-pyrazole-3-carboxylicacid

70 mg (0.26 mmol) of4-fluoro-1-(2-fluoro-phenyl)-5-methoxy-1H-pyrazole-3-carboxylic acidmethyl ester were dissolved in 1.3 ml of dioxane and 1.305 ml of a 1 Maqueous solution of lithium hydroxide were added. The mixture wasstirred at 56° C. for 30 min, then water and 2 N hydrochloric acid wereadded and the mixture extracted with diethyl ether. The organic phasewas evaporated to give 67 mg (33%) of the title compound.

SYNTHESIS EXAMPLE 201-(2-Fluoro-phenyl)-5-isopropoxy-1H-pyrazole-3-carboxylic acid

Step 1: Methyl1-(2-fluoro-phenyl)-5-isopropoxy-1H-pyrazole-3-carboxylate

150 mg (0.635 mmol) of1-(2-fluoro-phenyl)-5-hydroxy-1H-pyrazole-3-carboxylic acid methylester, 166.6 mg (0.635 mmol) of triphenylphosphine and 38.16 mg (0.635mmol) of 2-propanol were dissolved in 1.5 ml of DCM, and then a solutionof 0.635 mmol of di(4-chlorobenzyl) azodicarboxylate in 1.5 ml of DCMwas added. After stirring at room temperature for 4 h, the mixture wasfiltered and the solvent removed in vacuo. The obtained crude titlecompound was used in the hydrolysis step without further purification.

Step 2: 1-(2-Fluoro-phenyl)-5-isopropoxy-1H-pyrazole-3-carboxylic acid

The crude methyl1-(2-fluoro-phenyl)-5-isopropoxy-1H-pyrazole-3-carboxylate obtained instep 1 was dissolved in 6 ml of MOH, 2 ml of an aqueous 1 M solution ofsodium hydroxide were added, and the mixture was stirred for 5 h at 40°C. The solvent was removed and the residue subjected to acidic aqueouswork-up to give 70% of the title compound.

SYNTHESIS EXAMPLE 21(S)-3-{[1-(2-Fluoro-phenyl)-5-methoxy-1H-pyrazole-3-carbonyl]-amino}-3-(2-methyl-phenyl)-propionicacid amide

DMF (1.8 mg, 25 μmol) and oxalyl chloride (160 mg, 1.26 mmol) were addedto a solution of(S)-3-{[1-(2-fluoro-phenyl)-5-methoxy-1H-pyrazole-3-carbonyl]-amino}-3-(2-methyl-phenyl)-propionicacid (500 mg, 1.26 mmol) in DCM (5 ml) at room temperature. After 16 hat room temperature a 33% aqueous solution of ammonia (649 mg, 12.6mmol) was added and the mixture was stirred for further 16 h. Thesolvent was removed under reduced pressure and the residue was purifiedby preparative HPLC to give 170 mg (34%) of the title compound as acolorless oil.

SYNTHESIS EXAMPLE 22(S)-3-{[5-(3,3-Dimethyl-2-oxo-butoxy)-1-(2-fluoro-phenyl)-1H-pyrazole-3-carbonyl]-amino}-3-o-tolyl-propionicacid

Step 1:5-(3,3-Dimethyl-2-oxo-butoxy)-1-(2-fluoro-phenyl)-1H-pyrazole-3-carboxylicacid methyl ester

200 mg (0.85 mmol) of1-(2-fluoro-phenyl)-5-hydroxy-1H-pyrazole-3-carboxylic acid methyl esterwere dissolved in 5 ml of DMF. 552 mg (1.7 mmol) of cesium carbonate and152 mg (0.85 mmol) of 1-bromo-3,3-dimethyl-butan-2-one were added andthe mixture was heated to 50° C. for 6 h. Then the mixture was filteredand the solvent removed in vacuo. The obtained crude title compound wassubjected to hydrolysis without further purification.

Step 2:5-(3,3-Dimethyl-2-oxo-butoxy)-1-(2-fluoro-phenyl)-1H-pyrazole-3-carboxylicacid

100 mg (0.3 mmol) of5-(3,3-dimethyl-2-oxo-butoxy)-1-(2-fluoro-phenyl)-1H-pyrazole-3-carboxylicacid methyl ester were dissolved in 5 ml of MOH. 0.7 mmol of lithiumhydroxide and 2 ml of water were added and the mixture stirred overnightat room temperature. The solvent was removed in vacuo and the residuesubjected to aqueous work-up with a 10% solution of citric acid and DCM.The organic phase was dried and the solvent removed in vacuo to give thetitle compound.

Step 3:(S)-3-{[5-(3,3-Dimethyl-2-oxo-butoxy)-1-(2-fluoro-phenyl)-1H-pyrazole-3-carbonyl]-amino}-3-o-tolyl-propionicacid

324 mg (0.675 mmol) of5-(3,3-dimethyl-2-oxo-butoxy)-1-(2-fluoro-phenyl)-1H-pyrazole-3-carboxylicacid were dissolved in 5 ml of DMF and 0.675 mmol of TOTU and 1.35 mmolof EDIA were added. The mixture was stirred for 5 min at roomtemperature, then 0.675 mmol of(S)-3-amino-3-(2-methyl-phenyl)-propionic acid were added and themixture was stirred overnight at room temperature. After evaporation ofthe solvent, the residue was subjected to preparative HPLC to give thetitle compound in a yield of 67%.

Analogously as described in synthesis example 22, steps 1 and 2, thefollowing compounds were prepared, using chloro-acetone,1-bromo-butan-2-one and 2-bromo-1-cyclopropyl-ethanone, respectively,instead of 1-bromo-3,3-dimethyl-butan-2-one in step 1:

-   1-(2-fluoro-phenyl)-5-(2-oxo-propoxy)-1H-pyrazole-3-carboxylic acid-   1-(2-fluoro-phenyl)-5-(2-oxo-butoxy)-1H-pyrazole-3-carboxylic acid-   5-(2-cyclopropyl-2-oxo-ethoxy)-1-(2-fluoro-phenyl)-1H-pyrazole-3-carboxylic    acid

SYNTHESIS EXAMPLE 23(S)-3-{[1-(2-Fluoro-phenyl)-5-(2-hydroxy-3,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-3-o-tolyl-propionicacid

50 mg (0.1 mmol) of(S)-3-{[5-(3,3-dimethyl-2-oxo-butoxy)-1-(2-fluoro-phenyl)-1H-pyrazole-3-carbonyl]-amino}-3-o-tolyl-propionicacid were dissolved in 5 ml of DCM and 0.05 mmol of sodium borohydridewere added. The mixture was stirred at room temperature overnight. Thesolvent was removed in vacuo and the residue subjected to preparativeHPLC to given 52% of the title compound.

SYNTHESIS EXAMPLE 24(S)-3-{[1-(2-Fluoro-phenyl)-5-((R)-2-hydroxy-3,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-3-o-tolyl-propionicacid and(S)-3-{[1-(2-fluoro-phenyl)-5-((S)-2-hydroxy-3,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-3-o-tolyl-propionicacid

100 mg of(S)-3-{[1-(2-fluoro-phenyl)-5-(2-hydroxy-3,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-3-o-tolyl-propionicacid were separated into the two diastereomeric title compounds by HPLCon a chiral column (Chiralpak AD-H/55, 250×4.6 mm) at 30° C. (eluent:heptane/ethanol/MOH (15:1:1)+0.1% TFA; flow: 1.0 ml/min). 45 mg of thefirst diastereomer (retention time 16.35 min) eluted from the column and40 mg of the second diastereomer (retention time 21.15 min) eluted fromthe column were obtained, one of them being the diastereomer with Rconfiguration in the alcohol moiety and the other of them being thediastereomer with S configuration in the alcohol moiety (thestereochemistry in the alcohol moiety was not determined; it wasarbitrarily assigned R configuration in the first diastereomer elutedfrom the column and S configuration in the second diastereomer elutedfrom the column).

SYNTHESIS EXAMPLE 251-(2-Fluoro-phenyl)-5-(2-hydroxy-2,3,3-trimethyl-butoxy)-1H-pyrazole-3-carboxylicacid

610 mg (1.9 mmol) of5-(3,3-dimethyl-2-oxo-butoxy)-1-(2-fluoro-phenyl)-1H-pyrazole-3-carboxylicacid were dissolved in 20 ml of dry THF under argon and cooled to 0° C.1.4 ml of a 3 M solution of methylmagnesium bromide in diethyl ether(4.2 mmol) were added over 10 min. The mixture was allowed to reach roomtemperature overnight and then diluted with 50 ml of water and 30 ml ofEA. After phase separation, the aqueous phase was adjusted to pH=3 byaddition of 1 M hydrochloric acid. The precipitate which formed wasdissolved by addition of 40 ml of DCM, the organic phase was separated,dried over sodium sulfate and evaporated. 390 mg (61%) of the titlecompound were obtained.

Analogously as described in synthesis example 25, the followingcompounds were prepared, using ethylmagnesium bromide instead ofmethylmagnesium bromide in the case of5-(2-ethyl-2-hydroxy-butoxy)-1-(2-fluoro-phenyl)-1H-pyrazole-3-carboxylicacid:

-   1-(2-fluoro-phenyl)-5-(2-hydroxy-2-methyl-butoxy)-1H-pyrazole-3-carboxylic    acid-   1-(2-fluoro-phenyl)-5-(2-hydroxy-2-methyl-propoxy)-1H-pyrazole-3-carboxylic    acid-   5-(2-ethyl-2-hydroxy-butoxy)-1-(2-fluoro-phenyl)-1H-pyrazole-3-carboxylic    acid-   5-(2-cyclopropyl-2-hydroxy-propoxy)-1-(2-fluoro-phenyl)-1H-pyrazole-3-carboxylic    acid

SYNTHESIS EXAMPLE 26(S)-3-{[1-(2-Fluoro-phenyl)-5-((R)-2-hydroxy-2,3,3-trimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-3-o-tolyl-propionicacid and(S)-3-{[1-(2-fluoro-phenyl)-5-((S)-2-hydroxy-2,3,3-trimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-3-o-tolyl-propionicacid

390 mg (1.16 mmol) of1-(2-fluoro-phenyl)-5-(2-hydroxy-2,3,3-trimethyl-butoxy)-1H-pyrazole-3-carboxylic-acidwere dissolved in 6 ml of DMF, 380 mg of TOTU (1.16 mmol) and 420 mg ofNEM (3.6 mmol) were added and the mixture was stirred for 5 min at roomtemperature. Then 208 mg (1.16 mmol) of(S)-3-amino-3-(2-methyl-phenyl)-propionic acid were added and themixture was stirred overnight at room temperature. After evaporation ofthe solvent, the residue was subjected to preparative HPLC. 45 mg eachof the two diastereomeric title compounds were obtained, one of thembeing the diastereomer with R configuration in the alcohol moiety andthe other of them being the diastereomer with S configuration in thealcohol moiety (the stereochemistry in the alcohol moiety was notdetermined; it was arbitrarily assigned R configuration in the firstdiastereomer eluted from the column and S configuration in the seconddiastereomer eluted from the column).

SYNTHESIS EXAMPLE 27(S)-3-{[5-((R)-2-Cyclopropyl-2-hydroxy-propoxy)-1-(2-fluoro-phenyl)-1H-pyrazole-3-carbonyl]-amino}-3-o-tolyl-propionicacid and(S)-3-{[5-((S)-2-cyclopropyl-2-hydroxy-propoxy)-1-(2-fluoro-phenyl)-1H-pyrazole-3-carbonyl]-amino}-3-o-tolyl-propionicacid

100 mg of(S)-3-{[5-(2-cyclopropyl-2-hydroxy-propoxy)-1-(2-fluoro-phenyl)-1H-pyrazole-3-carbonyl]-amino}-3-o-tolyl-propionicwere separated into the two diastereomeric title compounds by HPLC on achiral column (Chiralpak OJ-H/59, 250×4.6 mm) at 30° C. (eluent:heptane/ethanol (10:1)+0.1% TFA; flow: 1.0 ml/min). 40 mg each of thetwo diastereomeric title compounds were obtained, one of them being thediastereomer with R configuration in the alcohol moiety and the other ofthem being the diastereomer with S configuration in the alcohol moiety(the stereochemistry in the alcohol moiety was not determined; it wasarbitrarily assigned R configuration in the first diastereomer(retention time 29.12 min) eluted from the column and S configuration inthe second diastereomer (retention time 36.36 min) eluted from thecolumn).

SYNTHESIS EXAMPLE 281-(2-Fluoro-phenyl)-5-methoxy-1H-pyrazole-3-carboxylic acid[(S)-2-(1,1-dimethyl-propylcarbamoyl)-1-o-tolyl-ethyl]-amide

79.4 mg (0.2 mmol, 1 Eq) of(S)-3-{[1-(2-Fluoro-phenyl)-5-methoxy-1H-pyrazole-3-carbonyl]-amino}-3-o-tolyl-propionicacid are dissolved in 4 ml of DMF, 5Eq of N-Ethylmorpholin and 1.1 Eq(0.22 mmol) of TOTU are added and the resulting mixture is stirred for10 minutes at RT. Then 0.22 mmol of 1,1-Dimethyl-propylamine are addedand the resulting mixture is stirred overnight at RT.

0.1 ml TFA was added, the mixture filtrated and subjected to HPLCchromatography to yield 40 mg of the product. (Yield: 43%).

Analogously as described in the synthesis examples, the examplecompounds of the formula I listed in Table 1 were prepared.

TABLE 1 Example compounds of the formula I m/z Rt LC/MS Activity ExampleCompound Name (1) (min) Method (2) 13-{[1-(2,5-Dimethyl-phenyl)-5-hydroxy-1H- 398.15 1.72 LC1 Cpyrazole-3-carbonyl]-amino}-3-(4-fluoro- phenyl)-propionic acid 23-[(5-Hydroxy-1-phenyl-1H-pyrazole-3- 318.15 2.87 LC3 Ccarbonyl)-amino]-hexanoic acid 3 3-[(5-Hydroxy-1-phenyl-1H-pyrazole-3-382.18 2.95 LC3 B carbonyl)-amino]-3-(4-methoxy-phenyl)- propionic acid4 3-[(5-Hydroxy-1-phenyl-1H-pyrazole-3- 304.13 2.70 LC3 Ccarbonyl)-amino]-3-methyl-butyric acid 5{1-[(5-Hydroxy-1-phenyl-1H-pyrazole-3- 330.15 2.87 LC3 Ccarbonyl)-amino]-cyclopentyl}-acetic acid 63-(3-tert-Butoxy-phenyl)-3-[(5-hydroxy-1- 424.16 2.99 LC8 Cphenyl-1H-pyrazole-3-carbonyl)-amino]- propionic acid 73-(3-tert-Butoxy-phenyl)-3-{[1-(2,5-dimethyl- 452.14 2.82 LC8 Cphenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid 83-{[1-(2,5-Dimethyl-phenyl)-5-hydroxy-1H- 332.11 2.72 LC8 Cpyrazole-3-carbonyl]-amino}-3-methyl- butyric acid 93-[(5-Hydroxy-1-phenyl-1H-pyrazole-3- 382.12 2.74 LC8 Bcarbonyl)-amino]-3-(3-methoxy-phenyl)- propionic acid 103-(3-Chloro-phenyl)-3-[(5-hydroxy-1-phenyl- 386.06 2.88 LC8 B1H-pyrazole-3-carbonyl)-amino]-propionic acid 113-(3,4-Dimethoxy-phenyl)-3-[(5-hydroxy-1- 412.13 2.61 LC8 Cphenyl-1H-pyrazole-3-carbonyl)-amino]- propionic acid 123-[(5-Hydroxy-1-phenyl-1H-pyrazole-3- 436.06 3.09 LC8 Bcarbonyl)-amino]-3-(4-trifluoromethoxy- phenyl)-propionic acid 133-[(5-Hydroxy-1-phenyl-1H-pyrazole-3- 318.12 2.64 LC8 Ccarbonyl)-amino]-4-methyl-pentanoic acid 143-[(5-Hydroxy-1-phenyl-1H-pyrazole-3- 332.13 2.82 LC8 Bcarbonyl)-amino]-heptanoic acid 15 3-[(5-Hydroxy-1-phenyl-1H-pyrazole-3-380.12 2.92 LC8 C carbonyl)-amino]-5-phenyl-pentanoic acid 163-[(5-Hydroxy-1-phenyl-1H-pyrazole-3- 353.1 2.06 LC8 Bcarbonyl)amino]-3-pyridin-3-yl-propionic acid 173-Cyclopropyl-3-[(5-hydroxy-1-phenyl-1H- 316.11 2.59 LC8 Cpyrazole-3-carbonyl)-amino]-propionic acid 183-Cyclohexyl-3-[(5-hydroxy-1-phenyl-1H- 358.14 2.95 LC8 Bpyrazole-3-carbonyl)-amino]-propionic acid 193-[(5-Hydroxy-1-phenyl-1H-pyrazole-3- 332.12 2.80 LC8 Bcarbonyl)-amino]-5-methyl-hexanoic acid 203-(2-Chloro-phenyl)-3-[(5-hydroxy-1-phenyl- 386.1 3.07 LC3 B1H-pyrazole-3-carbonyl)-amino]-propionic acid 213-[(5-Hydroxy-1-phenyl-1H-pyrazole-3- 366.12 3.16 LC8 Bcarbonyl)-amino]-3-o-tolyl-propionic acid 223-(4-Ethyl-phenyl)-3-[(5-hydroxy-1-phenyl- 380.13 2.98 LC8 B1H-pyrazole-3-carbonyl)-amino]-propionic acid 233-(4-tert-Butoxy-phenyl)-3-[(5-hydroxy-1- 424.2 3.18 LC3 Cphenyl-1H-pyrazole-3-carbonyl)-amino]- propionic acid 243-[(5-Hydroxy-1-phenyl-1H-pyrazole-3- 394.18 3.34 LC3 Bcarbonyl)-amino]-3-(4-isopropyl-phenyl)- propionic acid 253-[(5-Hydroxy-1-phenyl-1H-pyrazole-3- 410.19 3.09 LC3 Ccarbonyl)-amino]-3-(4-methoxy-2,3-dimethyl- phenyl)-propionic acid 263-{[1-(2,5-Dimethyl-phenyl)-5-hydroxy-1H- 346.18 2.95 LC3 Cpyrazole-3-carbonyl]-amino}-hexanoic acid 273-{[1-(2,5-Dimethyl-phenyl)-5-hydroxy-1H- 410.18 3.04 LC3 Cpyrazole-3-carbonyl]-amino}-3-(4-methoxy- phenyl)-propionic acid 283-{[1-(2,5-Dimethyl-phenyl)-5-hydroxy-1H- 410.12 2.86 LC8 Cpyrazole-3-carbonyl]-amino}-3-(3-methoxy- phenyl)-propionic acid 293-(3-Chloro-phenyl)-3-{[1-(2,5-dimethyl- 414.07 2.97 LC8 Cphenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid 303-(3,4-Dimethoxy-phenyl)-3-{[1-(2,5- 440.15 2.71 LC8 Cdimethyl-phenyl)-5-hydroxy-1H-pyrazole-3- carbonyl]-amino}-propionicacid 31 3-{[1-(2,5-Dimethyl-phenyl)-5-hydroxy-1H- 464.06 3.12 LC8 Cpyrazole-3-carbonyl]-amino}-3-(4- trifluoromethoxy-phenyl)-propionicacid 32 3-{[1-(2,5-Dimethyl-phenyl)-5-hydroxy-1H- 346.12 2.77 LC8 Cpyrazole-3-carbonyl]-amino}-4-methyl- pentanoic acid 333-{[1-(2,5-Dimethyl-phenyl)-5-hydroxy-1H- 360.13 2.93 LC8 Cpyrazole-3-carbonyl]-amino}-heptanoic acid 343-{[1-(2,5-Dimethyl-phenyl)-5-hydroxy-1H- 408.13 3.02 LC8 Cpyrazole-3-carbonyl]-amino}-5-phenyl- pentanoic acid 353-{[1-(2,5-Dimethyl-phenyl)-5-hydroxy-1H- 381.11 2.19 LC8 Cpyrazole-3-carbonyl]-amino}-3-pyridin-3-yl- propionic acid 363-Cyclopropyl-3-{[1-(2,5-dimethyl-phenyl)-5- 344.12 2.69 LC8 Chydroxy-1H-pyrazole-3-carbonyl]-amino}- propionic acid 373-Cyclohexyl-3-{[1-(2,5-dimethyl-phenyl)-5- 386.14 3.06 LC8 Chydroxy-1H-pyrazole-3-carbonyl]-amino}- propionic acid 383-{[1-(2,5-Dimethyl-phenyl)-5-hydroxy-1H- 360.13 2.90 LC8 Cpyrazole-3-carbonyl]-amino}-5-methyl- hexanoic acid 393-(2-Chloro-phenyl)-3-{[1-(2,5-dimethyl- 414.06 2.93 LC8 Cphenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid 403-{[1-(2,5-Dimethyl-phenyl)-5-hydroxy-1H- 394.13 2.93 LC8 Bpyrazole-3-carbonyl]-amino}-3-o-tolyl- propionic acid 413-{[1-(2,5-Dimethyl-phenyl)-5-hydroxy-1H- 408.14 3.07 LC8 Cpyrazole-3-carbonyl]-amino}-3-(4-ethyl- phenyl)-propionic acid 42(1-{[1-(2,5-Dimethyl-phenyl)-5-hydroxy-1H- 358.13 2.82 LC8 Cpyrazole-3-carbonyl]-amino}-cyclopentyl)- acetic acid 433-{[1-(2,5-Dimethyl-phenyl)-5-hydroxy-1H- 388.2 2.70 LC3 Cpyrazole-3-carbonyl]-amino}-3-(tetrahydro- pyran-4-yl)-propionic acid 443-Cyclopentyl-3-{[1-(2,5-dimethyl-phenyl)-5- 372.12 2.93 LC3 Chydroxy-1H-pyrazole-3-carbonyl]-amino}- propionic acid 453-(4-Chloro-phenyl)-3-{[1-(2,5-dimethyl- 414.16 3.22 LC3 Cphenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid 463-{[1-(2,5-Dimethyl-phenyl)-5-hydroxy-1H- 436.27 3.65 LC3 Cpyrazole-3-carbonyl]-amino}-3-(4-isobutyl- phenyl)-propionic acid 473-(3,4-Difluoro-phenyl)-3-{[1-(2,5-dimethyl- 416.16 3.20 LC3 Cphenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid 483-(3,4-Dichloro-phenyl)-3-{[1-(2,5-dimethyl- 448.13 3.43 LC3 Cphenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid 493-{[1-(2,5-Dimethyl-phenyl)-5-hydroxy-1H- 398.19 3.09 LC3 Cpyrazole-3-carbonyl]-amino}-3-(3-fluoro- phenyl)-propionic acid 503-{[1-(2,5-Dimethyl-phenyl)-5-hydroxy-1H- 394.22 3.18 LC3 Cpyrazole-3-carbonyl]-amino}-3-p-tolyl- propionic acid 513-{[1-(2,5-Dimethyl-phenyl)-5-hydroxy-1H- 394.21 3.17 LC3 Cpyrazole-3-carbonyl]-amino}-3-m-tolyl- propionic acid 523-(4-Cyano-phenyl)-3-{[1-(2,5-dimethyl- 405.2 3.00 LC3 Cphenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid 533-{[1-(2,5-Dimethyl-phenyl)-5-hydroxy-1H- 448.17 3.32 LC3 Cpyrazole-3-carbonyl]-amino}-3-(3- trifluoromethyl-phenyl)-propionic acid54 3-{[1-(2,5-Dimethyl-phenyl)-5-hydroxy-1H- 428.21 3.10 LC3 Cpyrazole-3-carbonyl]-amino}-3-(3-fluoro-4- methoxy-phenyl)-propionicacid 55 3-Biphenyl-4-yl-3-{[1-(2,5-dimethyl-phenyl)- 456.23 3.50 LC3 B5-hydroxy-1H-pyrazole-3-carbonyl]-amino}- propionic acid 563-(3,5-Difluoro-phenyl)-3-{[1-(2,5-dimethyl- 416.17 3.18 LC3 Cphenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid 573-{[1-(2,5-Dimethyl-phenyl)-5-hydroxy-1H- 448.17 3.39 LC3 Cpyrazole-3-carbonyl]-amino}-3-(4- trifluoromethyl-phenyl)-propionic acid58 3-(4-Chloro-phenyl)-3-[(5-hydroxy-1-phenyl- 386.18 2.91 LC8 B1H-pyrazole-3-carbonyl)-amino]-propionic acid 593-(3,5-Bis-trifluoromethyl-phenyl)-3-[(5- 488.15 3.21 LC8 Chydroxy-1-phenyl-1H-pyrazole-3-carbonyl)- amino]-propionic acid 603-(3,4-Difluoro-phenyl)-3-[(5-hydroxy-1- 388.19 2.83 LC8 Cphenyl-1H-pyrazole-3-carbonyl)-amino]- propionic acid 613-(4-Fluoro-phenyl)-3-[(5-hydroxy-1-phenyl- 370.17 3.00 LC3 C1H-pyrazole-3-carbonyl)-amino]-propionic acid 623-(3,4-Dichloro-phenyl)-3-[(5-hydroxy-1- 420.15 3.03 LC8 Bphenyl-1H-pyrazole-3-carbonyl)-amino]- propionic acid 633-(3-Fluoro-phenyl)-3-[(5-hydroxy-1-phenyl- 370.19 2.78 LC8 C1H-pyrazole-3-carbonyl)-amino]-propionic acid 643-[(5-Hydroxy-1-phenyl-1H-pyrazole-3- 366.23 2.86 LC8 Bcarbonyl)-amino]-3-p-tolyl-propionic acid 653-[(5-Hydroxy-1-phenyl-1H-pyrazole-3- 366.22 2.84 LC8 Bcarbonyl)-amino]-3-m-tolyl-propionic acid 663-(4-tert-Butyl-phenyl)-3-[(5-hydroxy-1- 408.22 3.45 LC3 Cphenyl-1H-pyrazole-3-carbonyl)-amino]- propionic acid 673-[(5-Hydroxy-1-phenyl-1H-pyrazole-3- 420.17 2.96 LC8 Bcarbonyl)-amino]-3-(3-trifluoromethyl- phenyl)-propionic acid 683-(3-Fluoro-4-methoxy-phenyl)-3-[(5- 400.18 2.93 LC3 Chydroxy-1-phenyl-1H-pyrazole-3-carbonyl)- amino]-propionic acid 693-Biphenyl-4-yl-3-[(5-hydroxy-1-phenyl-1H- 428.21 3.37 LC3 Bpyrazole-3-carbonyl)-amino]-propionic acid 703-(3,5-Difluoro-phenyl)-3-[(5-hydroxy-1- 388.18 2.83 LC8 Cphenyl-1H-pyrazole-3-carbonyl)-amino]- propionic acid 713-[(5-Hydroxy-1-phenyl-1H-pyrazole-3- 420.17 3.08 LC8 Ccarbonyl)-amino]-3-(4-trifluoromethyl- phenyl)-propionic acid 723-{[1-(3-Chloro-4-fluoro-phenyl)-5-hydroxy- 422.1 3.07 LC8 C1H-pyrazole-3-carbonyl]-amino}-3-(4-fluoro- phenyl)-propionic acid 733-{[1-(4-Chloro-phenyl)-5-hydroxy-1H- 804.92 4.22 LC2 Cpyrazole-3-carbonyl]-amino}-3-(4-fluoro- [(2M − H)⁻] phenyl)-propionicacid 74 (S)-3-{[1-(3-Fluoro-phenyl)-5-hydroxy-1H- 384.18 2.90 LC8 Apyrazole-3-carbonyl]-amino}-3-o-tolyl- propionic acid 75(S)-3-{[1-(3-Chloro-phenyl)-5-hydroxy-1H- 400.15 3.02 LC8 Bpyrazole-3-carbonyl]-amino}-3-o-tolyl- propionic acid 76(S)-3-{[1-(4-Fluoro-phenyl)-5-hydroxy-1H- 384.18 2.87 LC8 Apyrazole-3-carbonyl]-amino}-3-o-tolyl- propionic acid 77(S)-3-{[1-(2-Chloro-phenyl)-5-hydroxy-1H- 400.15 2.78 LC8 Apyrazole-3-carbonyl]-amino}-3-o-tolyl- propionic acid 783-{[1-(3,5-Dimethyl-phenyl)-5-hydroxy-1H- 394.19 3.05 LC8 Cpyrazole-3-carbonyl]-amino}-3-o-tolyl- propionic acid 793-{[1-(4-Chloro-phenyl)-5-hydroxy-1H- 400.12 3.02 LC8 Bpyrazole-3-carbonyl]-amino}-3-o-tolyl- propionic acid 803-{[1-(3-Chloro-4-fluoro-phenyl)-5-hydroxy- 418.11 3.09 LC8 B1H-pyrazole-3-carbonyl]-amino}-3-o-tolyl- propionic acid 81(S)-3-{[1-(2-Fluoro-phenyl)-5-hydroxy-1H- 384.18 2.74 LC8 Apyrazole-3-carbonyl]-amino}-3-o-tolyl- propionic acid 82(S)-3-[(5-Hydroxy-1-phenyl-1H-pyrazole-3- 366.21 3.04 LC3 Acarbonyl)-amino]-3-o-tolyl-propionic acid 83(R)-3-[(5-Hydroxy-1-phenyl-1H-pyrazole-3- 366.24 3.02 LC3 Ccarbonyl)-amino]-3-o-tolyl-propionic acid 843-(2,4-Dimethyl-phenyl)-3-[(5-hydroxy-1- 380.21 3.89 LC8 Bphenyl-1H-pyrazole-3-carbonyl)-amino]- propionic acid 853-(4-Fluoro-2-methyl-phenyl)-3-[(5-hydroxy- 384.12 3.09 LC3 B1-phenyl-1H-pyrazole-3-carbonyl)-amino]- propionic acid 863-(2,4-Difluoro-phenyl)-3-{[1-(4-fluoro- 406.06 2.87 LC8 Cphenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid 87(S)-3-{[5-Hydroxy-1-(4-methoxy-phenyl)-1H- 396.12 2.83 LC8 Bpyrazole-3-carbonyl]-amino}-3-o-tolyl- propionic acid 883-{[1-(3-Chloro-4-fluoro-phenyl)-5-hydroxy- 452.06 3.04 LC8 C1H-pyrazole-3-carbonyl]-amino}-3-(2-fluoro- 4-methoxy-phenyl)-propionicacid 89 3-(2,4-Dimethyl-phenyl)-3-{[1-(4-fluoro- 398.12 3.02 LC8 Bphenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid 903-(2-Fluoro-4-methoxy-phenyl)-3-{[1-(4- 418.1 2.87 LC8 Cfluoro-phenyl)-5-hydroxy-1H-pyrazole-3- carbonyl]-amino}-propionic acid91 3-{[1-(3-Chloro-4-fluoro-phenyl)-5-hydroxy- 432.1 3.20 LC8 C1H-pyrazole-3-carbonyl]-amino}-3-(2,4- dimethyl-phenyl)-propionic acid92 3-(2-Fluoro-4-methoxy-phenyl)-3-[(5- 400.1 2.81 LC8 Bhydroxy-1-phenyl-1H-pyrazole-3-carbonyl)- amino]-propionic acid 93(S)-3-{[1-(2-Fluoro-phenyl)-5-hydroxy-1H- 398.18 3.08 LC8pyrazole-3-carbonyl]-amino}-3-o-tolyl- propionic acid methyl ester 94(S)-3-{[5-Hydroxy-1-(3-methoxy-phenyl)-1H- 396.12 2.87 LC8 Bpyrazole-3-carbonyl]-amino}-3-o-tolyl- propionic acid 95(S)-3-(2,4-Dichloro-phenyl)-3-[(5-hydroxy-1- 420.02 3.06 LC8 Bphenyl-1H-pyrazole-3-carbonyl)-amino]- propionic acid 96(S)-3-(2-Fluoro-phenyl)-3-[(5-hydroxy-1- 370.08 2.80 LC8 Bphenyl-1H-pyrazole-3-carbonyl)-amino]- propionic acid 97(S)-3-[(5-Hydroxy-1-phenyl-1H-pyrazole-3- 420.06 2.96 LC8 Bcarbonyl)-amino]-3-(2-trifluoromethyl- phenyl)-propionic acid 98(S)-3-(4-Chloro-phenyl)-3-[(5-hydroxy-1- 386.06 2.95 LC8 Bphenyl-1H-pyrazole-3-carbonyl)-amino]- propionic acid 99(S)-3-[(5-Hydroxy-1-phenyl-1H-pyrazole-3- 420.09 3.04 LC8 Bcarbonyl)-amino]-3-(4-trifluoromethyl- phenyl)-propionic acid 100(S)-3-[(5-Hydroxy-1-phenyl-1H-pyrazole-3- 382.12 2.85 LC8 Bcarbonyl)-amino]-3-(2-methoxy-phenyl)- propionic acid 101(S)-3-(4-Cyano-phenyl)-3-[(5-hydroxy-1- 377.1 2.71 LC8 Bphenyl-1H-pyrazole-3-carbonyl)-amino]- propionic acid 1023-[(5-Hydroxy-1-phenyl-1H-pyrazole-3- 444.1 3.16 LC8 Bcarbonyl)-amino]-3-(4-phenoxy-phenyl)- propionic acid 103(S)-3-(2,6-Difluoro-phenyl)-3-[(5-hydroxy-1- 388.09 2.83 LC8 Bphenyl-1H-pyrazole-3-carbonyl)-amino]- propionic acid 1043-(4′-Fluoro-biphenyl-4-yl)-3-[(5-hydroxy-1- 446.13 3.17 LC8 Bphenyl-1H-pyrazole-3-carbonyl)-amino]- propionic acid 1053-[(5-Hydroxy-1-phenyl-1H-pyrazole-3- 418.11 2.30 LC8 Ccarbonyl)-amino]-3-(4-imidazol-1-yl-phenyl)- propionic acid 106(S)-3-{[1-(2-Chloro-phenyl)-5-hydroxy-1H- 454.01 3.06 LC8 Bpyrazole-3-carbonyl]-amino}-3-(2,4-dichloro- phenyl)-propionic acid 107(S)-3-{[1-(2-Chloro-phenyl)-5-hydroxy-1H- 404.05 2.78 LC8 Bpyrazole-3-carbonyl]-amino}-3-(2-fluoro- phenyl)-propionic acid 108(S)-3-{[1-(2-Chloro-phenyl)-5-hydroxy-1H- 454.02 2.91 LC8 Bpyrazole-3-carbonyl]-amino}-3-(2- trifluoromethyl-phenyl)-propionic acid109 (S)-3-(4-Chloro-phenyl)-3-{[1-(2-chloro- 420.03 2.91 LC8 Bphenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid 110(S)-3-{[1-(2-Chloro-phenyl)-5-hydroxy-1H- 454.05 3.00 LC8 Bpyrazole-3-carbonyl]-amino}-3-(4- trifluoromethyl-phenyl)-propionic acid111 (S)-3-{[1-(2-Chloro-phenyl)-5-hydroxy-1H- 414.03 3.90 LC2 Bpyrazole-3-carbonyl]-amino}-3-(2-methoxy- [(M − H)⁻] phenyl)-propionicacid 112 (S)-3-{[1-(2-Chloro-phenyl)-5-hydroxy-1H- 411.06 2.67 LC8 Bpyrazole-3-carbonyl]-amino}-3-(4-cyano- phenyl)-propionic acid 1133-{[1-(2-Chloro-phenyl)-5-hydroxy-1H- 478.08 3.12 LC8 Bpyrazole-3-carbonyl]-amino}-3-(4-phenoxy- phenyl)-propionic acid 114(S)-3-{[1-(2-Chloro-phenyl)-5-hydroxy-1H- 422.03 2.79 LC8 Bpyrazole-3-carbonyl]-amino}-3-(2,6-difluoro- phenyl)-propionic acid 1153-{[1-(2-Chloro-phenyl)-5-hydroxy-1H- 480.08 3.14 LC8 Apyrazole-3-carbonyl]-amino}-3-(4′-fluoro- biphenyl-4-yl)-propionic acid116 3-{[1-(2-Chloro-phenyl)-5-hydroxy-1H- 452.07 2.23 LC8 Cpyrazole-3-carbonyl]-amino}-3-(4-imidazol-1- yl-phenyl)-propionic acid117 (S)-3-(2,4-Dichloro-phenyl)-3-{[1-(2-fluoro- 438 3.40 LC8 Bphenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid 118(S)-3-(2-Fluoro-phenyl)-3-{[1-(2-fluoro- 388.11 2.96 LC8 Bphenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid 119(S)-3-{[1-(2-Fluoro-phenyl)-5-hydroxy-1H- 438.05 2.93 LC8 Bpyrazole-3-carbonyl]-amino}-3-(2- trifluoromethyl-phenyl)-propionic acid120 (S)-3-(4-Chloro-phenyl)-3-{[1-(2-fluoro- 404.06 2.86 LC8 Bphenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid 121(S)-3-{[1-(2-Fluoro-phenyl)-5-hydroxy-1H- 438.04 2.98 LC8 Bpyrazole-3-carbonyl]-amino}-3-(4- trifluoromethyl-phenyl)-propionic acid122 (S)-3-{[1-(2-Fluoro-phenyl)-5-hydroxy-1H- 400.14 2.77 LC8 Bpyrazole-3-carbonyl]-amino}-3-(2-methoxy- phenyl)-propionic acid 123(S)-3-(4-Cyano-phenyl)-3-{[1-(2-fluoro- 395.1 2.64 LC8 Bphenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid 1243-{[1-(2-Fluoro-phenyl)-5-hydroxy-1H- 462.11 3.08 LC8 Bpyrazole-3-carbonyl]-amino}-3-(4-phenoxy- phenyl)-propionic acid 125(S)-3-(2,6-Difluoro-phenyl)-3-{[1-(2-fluoro- 406.06 2.97 LC8 Bphenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid 1263-(4′-Fluoro-biphenyl-4-yl)-3-{[1-(2-fluoro- 464.13 3.14 LC8 Aphenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid 1273-{[1-(2-Fluoro-phenyl)-5-hydroxy-1H- 436.1 2.22 LC8 Cpyrazole-3-carbonyl]-amino}-3-(4-imidazol-1- yl-phenyl)-propionic acid128 (S)-3-{[1-(2-Fluoro-phenyl)-5-hydroxy-1H- 412.21 3.40 LC3pyrazole-3-carbonyl]-amino}-3-o-tolyl- propionic acid ethyl ester 129(S)-3-{[1-(2-Fluoro-phenyl)-5-methoxy-1H- 398.18 2.99 LC8 Apyrazole-3-carbonyl]-amino}-3-o-tolyl- propionic acid 130(S)-3-{[1-(5-Chloro-pyridin-2-yl)-5-hydroxy- 401.13 3.01 LC8 C1H-pyrazole-3-carbonyl]-amino}-3-o-tolyl- propionic acid 131(S)-3-{[1-(2-Chloro-pyridin-4-yl)-5-hydroxy- 401.15 3.07 LC3 B1H-pyrazole-3-carbonyl]-amino}-3-o-tolyl- propionic acid 1323-{[1-(2-Chloro-phenyl)-5-hydroxy-1H- 434.12 2.79 LC8 Bpyrazole-3-carbonyl]-amino}-3-(2-fluoro-4- methoxy-phenyl)-propionicacid 133 3-(2-Fluoro-4-methoxy-phenyl)-3-{[1-(2- 418.14 2.73 LC8 Bfluoro-phenyl)-5-hydroxy-1H-pyrazole-3- carbonyl]-amino}-propionic acid134 3-(4-Ethyl-phenyl)-3-{[1-(2-fluoro-phenyl)-5- 398.19 3.17 LC3 Bhydroxy-1H-pyrazole-3-carbonyl]-amino}- propionic acid 135(S)-3-{[1-(2-Chloro-phenyl)-5-hydroxy-1H- 400.16 3.05 LC3 Bpyrazole-3-carbonyl]-amino}-3-p-tolyl- propionic acid 136(S)-3-{[1-(2-Fluoro-phenyl)-5-hydroxy-1H- 401.18 2.60 LC3 Bpyrazole-3-carbonyl]-amino}-3-(6-methoxy- pyridin-3-yl)-propionic acid137 (S)-3-[(5-Hydroxy-1-phenyl-1H-pyrazole-3- 353.15 2.14 LC8 Bcarbonyl)-amino]-3-pyridin-3-yl-propionic acid 138(S)-3-{[5-Hydroxy-1-(4-trifluoromethyl- 436.17 2.78 LC8 Cpyrimidin-2-yl)-1H-pyrazole-3-carbonyl]- amino}-3-o-tolyl-propionic acid139 (S)-3-{[1-(2-Chloro-phenyl)-5-hydroxy-1H- 417.13 2.67 LC8 Bpyrazole-3-carbonyl]-amino}-3-(6-methoxy- pyridin-3-yl)-propionic acid140 (S)-3-{[1-(2-Fluoro-phenyl)-5-hydroxy-1H- 371.16 2.00 LC3 Bpyrazole-3-carbonyl]-amino}-3-pyridin-3-yl- propionic acid 141(S)-3-[(5-Hydroxy-1-pyridin-4-yl-1H- 367.19 2.18 LC3 Cpyrazole-3-carbonyl)-amino]-3-o-tolyl- propionic acid 1423-{[1-(2-Chloro-phenyl)-5-hydroxy-1H- 418.15 3.04 LC3 Bpyrazole-3-carbonyl]-amino}-3-(4-fluoro-2- methyl-phenyl)-propionic acid143 (S)-3-[(5-Hydroxy-1-pyridin-3-yl-1H- 367.18 2.25 LC8 Cpyrazole-3-carbonyl)-amino]-3-o-tolyl- propionic acid 144(S)-3-[(5-Hydroxy-1-phenyl-1H-pyrazole-3- 383.17 2.46 LC8 Bcarbonyl)-amino]-3-(6-methoxy-pyridin-3-yl)- propionic acid 145(S)-3-{[1-(2-Chloro-phenyl)-5-hydroxy-1H- 387.12 2.08 LC8 Bpyrazole-3-carbonyl]-amino}-3-pyridin-3-yl- propionic acid 146(S)-3-(4′-Fluoro-biphenyl-4-yl)-3-{[1-(2- 464.07 3.08 LC8 Cfluoro-phenyl)-5-hydroxy-1H-pyrazole-3- carbonyl]-amino}-propionic acid147 (R)-3-(4′-Fluoro-biphenyl-4-yl)-3-{[1-(2- 464.07 3.07 LC8 Afluoro-phenyl)-5-hydroxy-1H-pyrazole-3- carbonyl]-amino}-propionic acid148 (S)-3-{[1-(2-Chloro-phenyl)-5-hydroxy-1H- 480.05 3.25 LC8 Cpyrazole-3-carbonyl]-amino}-3-(4′-fluoro- biphenyl-4-yl)-propionic acid149 (R)-3-{[1-(2-Chloro-phenyl)-5-hydroxy-1H- 480.05 3.11 LC8 Apyrazole-3-carbonyl]-amino}-3-(4′-fluoro- biphenyl-4-yl)-propionic acid150 3-Biphenyl-4-yl-3-{[1-(2-fluoro-phenyl)-5- 446.16 3.05 LC8 Ahydroxy-1H-pyrazole-3-carbonyl]-amino}- propionic acid 1513-Biphenyl-4-yl-3-[(5-hydroxy-1-pyridin-4-yl- 429.16 2.63 LC8 C1H-pyrazole-3-carbonyl)-amino]-propionic acid 1523-{[1-(2-Chloro-phenyl)-5-hydroxy-1H- 506.12 3.63 LC8pyrazole-3-carbonyl]-amino}-3-(4-phenoxy- phenyl)-propionic acid ethylester 153 3-(4′-Fluoro-biphenyl-4-yl)-3-{[1-(2-fluoro- 492.12 3.47 LC8phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid ethylester 154 3-{[1-(2-Chloro-phenyl)-5-hydroxy-1H- 508.1 3.51 LC8pyrazole-3-carbonyl]-amino}-3-(4′-fluoro- biphenyl-4-yl)-propionic acidethyl ester 155 3-{[1-(2-Fluoro-phenyl)-5-hydroxy-1H- 490.14 3.49 LC8pyrazole-3-carbonyl]-amino}-3-(4-phenoxy- phenyl)-propionic acid ethylester 156 3-{[1-(2-Fluoro-phenyl)-5-hydroxy-1H- 476.14 3.03 LC8 Bpyrazole-3-carbonyl]-amino}-3-(3′-methoxy- biphenyl-4-yl)-propionic acid157 3-{[1-(2-Chloro-phenyl)-5-hydroxy-1H- 492.12 3.09 LC8 Bpyrazole-3-carbonyl]-amino}-3-(3′-methoxy- biphenyl-4-yl)-propionic acid158 3-Benzo[1,3]dioxol-4-yl-3-[(5-hydroxy-1- 396.18 2.95 LC3 Bphenyl-1H-pyrazole-3-carbonyl)-amino]- propionic acid 159(S)-3-(2-Bromo-phenyl)-3-[(5-hydroxy-1- 430.11 3.09 LC3 Bphenyl-1H-pyrazole-3-carbonyl)-amino]- propionic acid 160(S)-3-(3-Cyano-phenyl)-3-[(5-hydroxy-1- 377.18 2.87 LC3 Cphenyl-1H-pyrazole-3-carbonyl)-amino]- propionic acid 1613-(2,4-Dimethoxy-phenyl)-3-[(5-hydroxy-1- 412.21 3.05 LC3 Cphenyl-1H-pyrazole-3-carbonyl)-amino]- propionic acid 1623-(2-Chloro-4-methoxy-phenyl)-3-[(5- 416.18 3.10 LC3 Bhydroxy-1-phenyl-1H-pyrazole-3-carbonyl)- amino]-propionic acid 163(S)-3-(4-Fluoro-phenyl)-3-[(5-hydroxy-1- 370.18 3.00 LC3 Bphenyl-1H-pyrazole-3-carbonyl)-amino]- propionic acid 164(S)-3-(2,3-Dichloro-phenyl)-3-[(5-hydroxy-1- 420.11 3.22 LC3 Aphenyl-1H-pyrazole-3-carbonyl)-amino]- propionic acid 165(S)-3-[(5-Hydroxy-1-phenyl-1H-pyrazole-3- 382.19 2.93 LC3 Ccarbonyl)-amino]-3-(3-methoxy-phenyl)- propionic acid 166(S)-3-(3-Fluoro-phenyl)-3-[(5-hydroxy-1- 370.17 3.04 LC3 Cphenyl-1H-pyrazole-3-carbonyl)-amino]- propionic acid 167(S)-3-(3-Chloro-phenyl)-3-[(5-hydroxy-1- 386.15 3.10 LC3 Bphenyl-1H-pyrazole-3-carbonyl)-amino]- propionic acid 1683-(2,3-Dichloro-phenyl)-3-[(5-hydroxy-1- 420.11 3.22 LC3 Bphenyl-1H-pyrazole-3-carbonyl)-amino]- propionic acid 169(2R,3R)-2-Hydroxy-3-[(5-hydroxy-1-phenyl- 398.2 2.79 LC3 C1H-pyrazole-3-carbonyl)-amino]-3-(2- methoxy-phenyl)-propionic acid 170(S)-3-(2,3-Dimethoxy-phenyl)-3-[(5-hydroxy- 412.21 2.99 LC3 B1-phenyl-1H-pyrazole-3-carbonyl)-amino]- propionic acid 1713-(3′-Fluoro-biphenyl-4-yl)-3-[(5-hydroxy-1- 446.22 3.43 LC3 Bphenyl-1H-pyrazole-3-carbonyl)-amino]- propionic acid 1723-(3-Chloro-2-fluoro-phenyl)-3-[(5-hydroxy- 404.14 3.18 LC3 B1-phenyl-1H-pyrazole-3-carbonyl)-amino]- propionic acid 1733-[3-(4-Chloro-phenoxy)-phenyl]-3-[(5- 478.18 3.54 LC3 Chydroxy-1-phenyl-1H-pyrazole-3-carbonyl)- amino]-propionic acid 1743-Benzo[1,3]dioxol-4-yl-3-{[1-(2,4-difluoro- 432.19 2.95 LC3 Bphenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid 175(S)-3-(2-Bromo-phenyl)-3-{[1-(2,4-difluoro- 466.1 3.07 LC3 Bphenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid 176(S)-3-(4-Cyano-phenyl)-3-{[1-(2,4-difluoro- 413.17 2.85 LC3 Bphenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid 177(S)-3-{[1-(2,4-Difluoro-phenyl)-5-hydroxy- 418.17 3.00 LC3 B1H-pyrazole-3-carbonyl]-amino}-3-(2- methoxy-phenyl)-propionic acid 1783-(5-Chloro-2-methoxy-phenyl)-3-{[1-(2,4- 452.16 3.22 LC3 Cdifluoro-phenyl)-5-hydroxy-1H-pyrazole-3- carbonyl]-amino}-propionicacid 179 3-(2-Chloro-4-methoxy-phenyl)-3-{[1-(2,4- 452.17 3.09 LC3 Bdifluoro-phenyl)-5-hydroxy-1H-pyrazole-3- carbonyl]-amino}-propionicacid 180 (S)-3-{[1-(2,4-Difluoro-phenyl)-5-hydroxy- 406.17 2.97 LC3 B1H-pyrazole-3-carbonyl]-amino}-3-(4-fluoro- phenyl)-propionic acid 181(S)-3-(2,3-Dichloro-phenyl)-3-{[1-(2,4- 456.11 3.20 LC3 Adifluoro-phenyl)-5-hydroxy-1H-pyrazole-3- carbonyl]-amino}-propionicacid 182 (S)-3-{[1-(2,4-Difluoro-phenyl)-5-hydroxy- 418.18 2.95 LC3 B1H-pyrazole-3-carbonyl]-amino}-3-(3- methoxy-phenyl)-propionic acid 183(S)-3-{[1-(2,4-Difluoro-phenyl)-5-hydroxy- 406.14 3.04 LC3 B1H-pyrazole-3-carbonyl]-amino}-3-(3-fluoro- phenyl)-propionic acid 184(S)-3-(3-Chloro-phenyl)-3-{[1-(2,4-difluoro- 422.14 3.12 LC3 Bphenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid 185(S)-3-{[1-(2,4-Difluoro-phenyl)-5-hydroxy- 456.16 3.24 LC3 B1H-pyrazole-3-carbonyl]-amino}-3-(4- trifluoromethyl-phenyl)-propionicacid 186 3-(2,3-Dichloro-phenyl)-3-{[1-(2,4-difluoro- 456.11 3.18 LC3 Bphenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid 1873-{[1-(2,4-Difluoro-phenyl)-5-hydroxy-1H- 472.16 3.29 LC3 Bpyrazole-3-carbonyl]-amino}-3-(4- trifluoromethoxy-phenyl)-propionicacid 188 (2R,3R)-3-{[1-(2,4-Difluoro-phenyl)-5- 434.17 2.79 LC3 Chydroxy-1H-pyrazole-3-carbonyl]-amino}-2-hydroxy-3-(2-methoxy-phenyl)-propionic acid 189(S)-3-{[1-(2,4-Difluoro-phenyl)-5-hydroxy- 448.21 3.04 LC3 B1H-pyrazole-3-carbonyl]-amino}-3-(2,3- dimethoxy-phenyl)-propionic acid190 (S)-3-{[1-(2,4-Difluoro-phenyl)-5-hydroxy- 402.19 3.05 LC3 B1H-pyrazole-3-carbonyl]-amino}-3-m-tolyl- propionic acid 1913-{[1-(2,4-Difluoro-phenyl)-5-hydroxy-1H- 416.2 3.14 LC3 Apyrazole-3-carbonyl]-amino}-3-(2,3-dimethyl- phenyl)-propionic acid 1923-(3-Chloro-2-fluoro-phenyl)-3-{[1-(2,4- 440.11 3.18 LC3 Bdifluoro-phenyl)-5-hydroxy-1H-pyrazole-3- carbonyl]-amino}-propionicacid 193 3-(2-Chloro-3-trifluoromethyl-phenyl)-3-{[1- 490.13 3.30 LC3 B(2,4-difluoro-phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]-amino}-propionic acid 1943-{[1-(2,4-Difluoro-phenyl)-5-hydroxy-1H- 416.21 3.24 LC3 Bpyrazole-3-carbonyl]-amino}-3-(4-ethyl- phenyl)-propionic acid 1953-{[1-(2,4-Difluoro-phenyl)-5-hydroxy-1H- 416.21 3.18 LC3 Bpyrazole-3-carbonyl]-amino}-3-(2,4-dimethyl- phenyl)-propionic acid 1963-{[1-(2,4-Difluoro-phenyl)-5-hydroxy-1H- 420.18 3.07 LC3 Apyrazole-3-carbonyl]-amino}-3-(4-fluoro-2- methyl-phenyl)-propionic acid197 3-Biphenyl-4-yl-3-{[1-(2,4-difluoro-phenyl)-5- 464.22 3.39 LC3 Bhydroxy-1H-pyrazole-3-carbonyl]-amino}- propionic acid 198(S)-3-{[1-(2,4-Difluoro-phenyl)-5-hydroxy- 456.14 3.15 LC3 B1H-pyrazole-3-carbonyl]-amino}-3-(2- trifluoromethyl-phenyl)-propionicacid 199 3-{[1-(2,4-Difluoro-phenyl)-5-hydroxy-1H- 480.21 3.37 LC3 Bpyrazole-3-carbonyl]-amino}-3-(4-phenoxy- phenyl)-propionic acid 200(S)-3-(4-Chloro-phenyl)-3-{[1-(2,4-difluoro- 422.14 3.12 LC3 Bphenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid 201(S)-3-(2,4-Dichloro-phenyl)-3-{[1-(2,4- 456.11 3.25 LC3 Bdifluoro-phenyl)-5-hydroxy-1H-pyrazole-3- carbonyl]-amino}-propionicacid 202 3-{[1-(2,4-Difluoro-phenyl)-5-hydroxy-1H- 482.22 3.42 LC3 Bpyrazole-3-carbonyl]-amino}-3-(4′-fluoro- biphenyl-4-yl)-propionic acid203 3-{[1-(2-Chloro-phenyl)-5-hydroxy-1H- 430.18 2.99 LC3 Bpyrazole-3-carbonyl]-amino}-3-(4-methoxy- 2-methyl-phenyl)-propionicacid 204 (S)-3-(2-Bromo-phenyl)-3-{[1-(2-chloro- 464.04 3.05 LC3 Bphenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid 205(S)-3-{[1-(2-Chloro-phenyl)-5-hydroxy-1H- 411.12 2.84 LC3 Bpyrazole-3-carbonyl]-amino}-3-(3-cyano- phenyl)-propionic acid 2063-{[1-(2-Chloro-phenyl)-5-hydroxy-1H- 454.12 3.17 LC3 Bpyrazole-3-carbonyl]-amino}-3-(3- trifluoromethyl-phenyl)-propionic acid207 3-{[1-(2-Chloro-phenyl)-5-hydroxy-1H- 446.18 3.00 LC3 Bpyrazole-3-carbonyl]-amino}-3-(2,4- dimethoxy-phenyl)-propionic acid 2083-{[1-(2-Chloro-phenyl)-5-hydroxy-1H- 404.11 2.97 LC3 Bpyrazole-3-carbonyl]-amino}-3-(2-fluoro- phenyl)-propionic acid 2093-(5-Chloro-2-methoxy-phenyl)-3-{[1-(2- 450.11 3.14 LC3 Bchloro-phenyl)-5-hydroxy-1H-pyrazole-3- carbonyl]-amino}-propionic acid210 3-(2-Chloro-4-methoxy-phenyl)-3-{[1-(2- 450.15 3.05 LC3 Bchloro-phenyl)-5-hydroxy-1H-pyrazole-3- carbonyl]-amino}-propionic acid211 (S)-3-{[1-(2-Chloro-phenyl)-5-hydroxy-1H- 404.12 2.99 LC3 Bpyrazole-3-carbonyl]-amino}-3-(4-fluoro- phenyl)-propionic acid 212(S)-3-{[1-(2-Chloro-phenyl)-5-hydroxy-1H- 454.06 3.17 LC3 Apyrazole-3-carbonyl]-amino}-3-(2,3-dichloro- phenyl)-propionic acid 213(S)-3-{[1-(2-Chloro-phenyl)-5-hydroxy-1H- 416.15 2.90 LC3 Bpyrazole-3-carbonyl]-amino}-3-(3-methoxy- phenyl)-propionic acid 214(S)-3-(3-Chloro-phenyl)-3-{[1-(2-chloro- 420.09 3.07 LC3 Bphenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid 2153-{[1-(2-Chloro-phenyl)-5-hydroxy-1H- 470.12 3.32 LC3 Bpyrazole-3-carbonyl]-amino}-3-(4- trifluoromethoxy-phenyl)-propionicacid 216 (2R,3R)-3-{[1-(2-Chloro-phenyl)-5-hydroxy- 432.13 2.74 LC3 C1H-pyrazole-3-carbonyl]-amino}-2-hydroxy- 3-(2-methoxy-phenyl)-propionicacid 217 (S)-3-{[1-(2-Chloro-phenyl)-5-hydroxy-1H- 400.15 3.02 LC3 Bpyrazole-3-carbonyl]-amino}-3-m-tolyl- propionic acid 218(S)-3-{[1-(2-Chloro-phenyl)-5-hydroxy-1H- 454.12 3.20 LC3 Bpyrazole-3-carbonyl]-amino}-3-(3- trifluoromethyl-phenyl)-propionic acid219 3-{[1-(2-Chloro-phenyl)-5-hydroxy-1H- 480.19 3.40 LC3 Bpyrazole-3-carbonyl]-amino}-3-(3′-fluoro- biphenyl-4-yl)-propionic acid220 3-{[1-(2-Chloro-phenyl)-5-hydroxy-1H- 414.18 3.12 LC3 Bpyrazole-3-carbonyl]-amino}-3-(2,3-dimethyl- phenyl)-propionic acid 2213-{[1-(2-Chloro-phenyl)-5-hydroxy-1H- 472.14 3.22 LC3 Bpyrazole-3-carbonyl]-amino}-3-(2-fluoro-3-trifluoromethyl-phenyl)-propionic acid 2223-(3-Chloro-2-fluoro-phenyl)-3-{[1-(2-chloro- 438.08 3.10 LC3 Bphenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid 2233-{[1-(2-Chloro-phenyl)-5-hydroxy-1H- 488.08 3.29 LC3 Bpyrazole-3-carbonyl]-amino}-3-(2-chloro-3-trifluoromethyl-phenyl)-propionic acid 2243-{[1-(2-Chloro-phenyl)-5-hydroxy-1H- 414.16 3.18 LC3 Bpyrazole-3-carbonyl]-amino}-3-(4-ethyl- phenyl)-propionic acid 2253-{[1-(2-Chloro-phenyl)-5-hydroxy-1H- 414.16 3.12 LC3 Bpyrazole-3-carbonyl]-amino}-3-(2,4-dimethyl- phenyl)-propionic acid 2263-Biphenyl-4-yl-3-{[1-(2-chloro-phenyl)-5- 462.2 3.39 LC3 Bhydroxy-1H-pyrazole-3-carbonyl]-amino}- propionic acid 2273-{[1-(2-Chloro-phenyl)-5-hydroxy-1H- 454.06 3.29 LC3 Bpyrazole-3-carbonyl]-amino}-3-(3,4-dichloro- phenyl)-propionic acid 2283-Benzo[1,3]dioxol-4-yl-3-{[1-(2-fluoro- 414.16 2.89 LC3 Bphenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid 2293-(3-Benzyloxy-phenyl)-3-{[1-(2-fluoro- 476.21 3.32 LC3 Cphenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid 230(S)-3-(3-Cyano-phenyl)-3-{[1-(2-fluoro- 395.15 2.77 LC3 Bphenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid 2313-{[1-(2-Fluoro-phenyl)-5-hydroxy-1H- 438.14 3.14 LC3 Bpyrazole-3-carbonyl]-amino}-3-(3- trifluoromethyl-phenyl)-propionic acid232 3-(2,4-Dimethoxy-phenyl)-3-{[1-(2-fluoro- 430.2 2.97 LC3 Bphenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid 2333-(2-Fluoro-phenyl)-3-{[1-(2-fluoro-phenyl)- 388.14 2.87 LC3 B5-hydroxy-1H-pyrazole-3-carbonyl]-amino}- propionic acid 2343-(5-Chloro-2-methoxy-phenyl)-3-{[1-(2- 434.14 3.07 LC3 Bfluoro-phenyl)-5-hydroxy-1H-pyrazole-3- carbonyl]-amino}-propionic acid235 3-(2-Chloro-4-methoxy-phenyl)-3-{[1-(2- 434.17 3.05 LC3 Bfluoro-phenyl)-5-hydroxy-1H-pyrazole-3- carbonyl]-amino}-propionic acid236 (S)-3-(4-Fluoro-phenyl)-3-{[1-(2-fluoro- 388.16 2.90 LC3 Bphenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid 237(S)-3-{[1-(2-Fluoro-phenyl)-5-hydroxy-1H- 400.18 2.85 LC3 Bpyrazole-3-carbonyl]-amino}-3-(3-methoxy- phenyl)-propionic acid 2383-{[1-(2-Fluoro-phenyl)-5-hydroxy-1H- 456.16 3.22 LC3 Bpyrazole-3-carbonyl]-amino}-3-(2-fluoro-4-trifluoromethyl-phenyl)-propionic acid 2393-{[1-(2-Fluoro-phenyl)-5-hydroxy-1H- 454.17 3.24 LC3 Bpyrazole-3-carbonyl]-amino}-3-(4- trifluoromethoxy-phenyl)-propionicacid 240 (2R,3R)-3-{[1-(2-Fluoro-phenyl)-5-hydroxy- 416.17 2.72 LC3 C1H-pyrazole-3-carbonyl]-amino}-2-hydroxy- 3-(2-methoxy-phenyl)-propionicacid 241 (S)-3-{[1-(2-Fluoro-phenyl)-5-hydroxy-1H- 438.14 3.17 LC3 Bpyrazole-3-carbonyl]-amino}-3-(3- trifluoromethyl-phenyl)-propionic acid242 3-(3′-Fluoro-biphenyl-4-yl)-3-{[1-(2-fluoro- 464.22 3.35 LC3 Bphenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid 2433-(4-Chloro-2-fluoro-phenyl)-3-{[1-(2-fluoro- 422.13 3.09 LC3 Bphenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid 2443-(3-Chloro-2-fluoro-phenyl)-3-{[1-(2-fluoro- 422.11 3.04 LC3 Bphenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid 2453-(2-Chloro-3-trifluoromethyl-phenyl)-3-{[1- 472.11 3.22 LC3 B(2-fluoro-phenyl)-5-hydroxy-1H-pyrazole-3- carbonyl]-amino}-propionicacid 246 3-[3-(4-Chloro-phenoxy)-phenyl]-3-{[1-(2- 496.16 3.50 LC3 Bfluoro-phenyl)-5-hydroxy-1H-pyrazole-3- carbonyl]-amino}-propionic acid247 3-(2,4-Dimethyl-phenyl)-3-{[1-(2-fluoro- 398.2 3.09 LC3 Bphenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid 2483-(4-Fluoro-2-methyl-phenyl)-3-{[1-(2-fluoro- 402.18 3.02 LC3 Bphenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid 2493-Benzo[1,3]dioxol-4-yl-3-{[1-(3-chloro- 430.14 3.24 LC3 Bphenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid 2503-{[1-(3-Chloro-phenyl)-5-hydroxy-1H- 430.19 3.24 LC3 Bpyrazole-3-carbonyl]-amino}-3-(4-methoxy- 2-methyl-phenyl)-propionicacid 251 (S)-3-(2-Bromo-phenyl)-3-{[1-(3-chloro- 464.07 3.30 LC3 Bphenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid 252(S)-3-{[1-(3-Chloro-phenyl)-5-hydroxy-1H- 411.14 3.12 LC3 Cpyrazole-3-carbonyl]-amino}-3-(3-cyano- phenyl)-propionic acid 253(S)-3-{[1-(3-Chloro-phenyl)-5-hydroxy-1H- 416.16 3.25 LC3 Bpyrazole-3-carbonyl]-amino}-3-(2-methoxy- phenyl)-propionic acid 2543-{[1-(3-Chloro-phenyl)-5-hydroxy-1H- 404.13 3.20 LC3 Bpyrazole-3-carbonyl]-amino}-3-(2-fluoro- phenyl)-propionic acid 2553-(5-Chloro-2-methoxy-phenyl)-3-{[1-(3- 450.13 3.42 LC3 Bchloro-phenyl)-5-hydroxy-1H-pyrazole-3- carbonyl]-amino}-propionic acid256 (S)-3-{[1-(3-Chloro-phenyl)-5-hydroxy-1H- 454.13 3.43 LC3 Cpyrazole-3-carbonyl]-amino}-3-(4- trifluoromethyl-phenyl)-propionic acid257 3-{[1-(3-Chloro-phenyl)-5-hydroxy-1H- 454.09 3.43 LC3 Bpyrazole-3-carbonyl]-amino}-3-(2,3-dichloro- phenyl)-propionic acid 258(S)-3-{[1-(3-Chloro-phenyl)-5-hydroxy-1H- 400.17 3.29 LC3 Bpyrazole-3-carbonyl]-amino}-3-m-tolyl- propionic acid 259(S)-3-{[1-(3-Chloro-phenyl)-5-hydroxy-1H- 454.13 3.45 LC3 Cpyrazole-3-carbonyl]-amino}-3-(3- trifluoromethyl-phenyl)-propionic acid260 3-{[1-(3-Chloro-phenyl)-5-hydroxy-1H- 480.19 3.62 LC3 Cpyrazole-3-carbonyl]-amino}-3-(3′-fluoro- biphenyl-4-yl)-propionic acid261 3-{[1-(3-Chloro-phenyl)-5-hydroxy-1H- 414.18 3.39 LC3 Bpyrazole-3-carbonyl]-amino}-3-(2,3-dimethyl- phenyl)-propionic acid 2623-(3-Chloro-2-fluoro-phenyl)-3-{[1-(3-chloro- 438.1 3.37 LC3 Bphenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid 2633-{[1-(3-Chloro-phenyl)-5-hydroxy-1H- 488.09 3.49 LC3 Bpyrazole-3-carbonyl]-amino}-3-(2-chloro-3-trifluoromethyl-phenyl)-propionic acid 2643-{[1-(3-Chloro-phenyl)-5-hydroxy-1H- 414.18 3.43 LC3 Bpyrazole-3-carbonyl]-amino}-3-(4-ethyl- phenyl)-propionic acid 265(S)-3-{[1-(3-Chloro-phenyl)-5-hydroxy-1H- 422.14 3.24 LC3 Bpyrazole-3-carbonyl]-amino}-3-(2,6-difluoro- phenyl)-propionic acid 266(S)-3-{[1-(3-Chloro-phenyl)-5-hydroxy-1H- 454.09 3.52 LC3 Bpyrazole-3-carbonyl]-amino}-3-(2,4-dichloro- phenyl)-propionic acid 2673-{[1-(3-Chloro-phenyl)-5-hydroxy-1H- 480.16 3.65 LC3 Cpyrazole-3-carbonyl]-amino}-3-(4′-fluoro- biphenyl-4-yl)-propionic acid268 (S)-3-{[1-(3-Chloro-phenyl)-5-hydroxy-1H- 387.13 2.37 LC3 Cpyrazole-3-carbonyl]-amino}-3-pyridin-3-yl- propionic acid 269(S)-3-{[1-(3-Chloro-phenyl)-5-hydroxy-1H- 417.13 2.87 LC3 Cpyrazole-3-carbonyl]-amino}-3-(6-methoxy- pyridin-3-yl)-propionic acid270 (S)-3-(2-Bromo-phenyl)-3-{[1-(4-chloro- 464.05 3.30 LC3 Bphenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid 271(S)-3-{[1-(4-Chloro-phenyl)-5-hydroxy-1H- 411.12 3.15 LC3 Cpyrazole-3-carbonyl]-amino}-3-(3-cyano- phenyl)-propionic acid 272(S)-3-{[1-(4-Chloro-phenyl)-5-hydroxy-1H- 411.13 3.10 LC3 Cpyrazole-3-carbonyl]-amino}-3-(4-cyano- phenyl)-propionic acid 2733-{[1-(4-Chloro-phenyl)-5-hydroxy-1H- 446.16 3.29 LC3 Cpyrazole-3-carbonyl]-amino}-3-(2,4- dimethoxy-phenyl)-propionic acid 274(S)-3-{[1-(4-Chloro-phenyl)-5-hydroxy-1H- 416.14 3.27 LC3 Cpyrazole-3-carbonyl]-amino}-3-(2-methoxy- phenyl)-propionic acid 2753-(5-Chloro-2-methoxy-phenyl)-3-{[1-(4- 450.11 3.45 LC3 Cchloro-phenyl)-5-hydroxy-1H-pyrazole-3- carbonyl]-amino}-propionic acid276 (S)-3-{[1-(4-Chloro-phenyl)-5-hydroxy-1H- 404.13 3.22 LC3 Cpyrazole-3-carbonyl]-amino}-3-(4-fluoro- phenyl)-propionic acid 277(S)-3-{[1-(4-Chloro-phenyl)-5-hydroxy-1H- 454.06 3.49 LC3 Bpyrazole-3-carbonyl]-amino}-3-(2,3-dichloro- phenyl)-propionic acid 278(S)-3-{[1-(4-Chloro-phenyl)-5-hydroxy-1H- 416.15 3.18 LC3 Cpyrazole-3-carbonyl]-amino}-3-(3-methoxy- phenyl)-propionic acid 279(S)-3-{[1-(4-Chloro-phenyl)-5-hydroxy-1H- 404.12 3.24 LC3 Cpyrazole-3-carbonyl]-amino}-3-(3-fluoro- phenyl)-propionic acid 280(S)-3-(3-Chloro-phenyl)-3-{[1-(4-chloro- 420.1 3.35 LC3 Cphenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid 2813-{[1-(4-Chloro-phenyl)-5-hydroxy-1H- 454.07 3.42 LC3 Bpyrazole-3-carbonyl]-amino}-3-(2,3-dichloro- phenyl)-propionic acid 282(2R,3R)-3-{[1-(4-Chloro-phenyl)-5-hydroxy- 432.15 3.04 LC3 C1H-pyrazole-3-carbonyl]-amino}-2-hydroxy- 3-(2-methoxy-phenyl)-propionicacid 283 (S)-3-{[1-(4-Chloro-phenyl)-5-hydroxy-1H- 446.17 3.22 LC3 Bpyrazole-3-carbonyl]-amino}-3-(2,3- dimethoxy-phenyl)-propionic acid 284(S)-3-{[1-(4-Chloro-phenyl)-5-hydroxy-1H- 400.15 3.30 LC3 Bpyrazole-3-carbonyl]-amino}-3-m-tolyl- propionic acid 285(S)-3-{[1-(4-Chloro-phenyl)-5-hydroxy-1H- 454.12 3.43 LC3 Cpyrazole-3-carbonyl]-amino}-3-(3- trifluoromethyl-phenyl)-propionic acid286 3-(4-Chloro-2-fluoro-phenyl)-3-{[1-(4-chloro- 438.1 3.40 LC3 Cphenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid 2873-{[1-(4-Chloro-phenyl)-5-hydroxy-1H- 414.17 3.43 LC3 Bpyrazole-3-carbonyl]-amino}-3-(2,3-dimethyl- phenyl)-propionic acid 2883-(3-Chloro-2-fluoro-phenyl)-3-{[1-(4-chloro- 438.1 3.42 LC3 Cphenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid 2893-{[1-(4-Chloro-phenyl)-5-hydroxy-1H- 488.09 3.50 LC3 Bpyrazole-3-carbonyl]-amino}-3-(2-chloro-3-trifluoromethyl-phenyl)-propionic acid 2903-[3-(4-Chloro-phenoxy)-phenyl]-3-{[1-(4- 512.14 3.77 LC3 Cchloro-phenyl)-5-hydroxy-1H-pyrazole-3- carbonyl]-amino}-propionic acid291 3-{[1-(4-Chloro-phenyl)-5-hydroxy-1H- 414.17 3.40 LC3 Bpyrazole-3-carbonyl]-amino}-3-(2,4-dimethyl- phenyl)-propionic acid 2923-{[1-(4-Chloro-phenyl)-5-hydroxy-1H- 418.15 3.37 LC3 Bpyrazole-3-carbonyl]-amino}-3-(4-fluoro-2- methyl-phenyl)-propionic acid293 (S)-3-{[1-(4-Chloro-phenyl)-5-hydroxy-1H- 404.13 3.25 LC3 Cpyrazole-3-carbonyl]-amino}-3-(2-fluoro- phenyl)-propionic acid 2943-{[1-(4-Chloro-phenyl)-5-hydroxy-1H- 478.18 3.60 LC3 Cpyrazole-3-carbonyl]-amino}-3-(4-phenoxy- phenyl)-propionic acid 295(S)-3-{[1-(4-Chloro-phenyl)-5-hydroxy-1H- 422.12 3.25 LC3 Cpyrazole-3-carbonyl]-amino}-3-(2,6-difluoro- phenyl)-propionic acid 296(S)-3-(4-Chloro-phenyl)-3-{[1-(4-chloro- 420.11 3.37 LC3 Bphenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid 297(S)-3-{[1-(4-Chloro-phenyl)-5-hydroxy-1H- 454.07 3.49 LC3 Bpyrazole-3-carbonyl]-amino}-3-(2,4-dichloro- phenyl)-propionic acid 298(S)-3-{[1-(4-Chloro-phenyl)-5-hydroxy-1H- 387.14 2.42 LC3 Cpyrazole-3-carbonyl]-amino}-3-pyridin-3-yl- propionic acid 299(S)-3-{[1-(4-Chloro-phenyl)-5-hydroxy-1H- 417.14 2.92 LC3 Cpyrazole-3-carbonyl]-amino}-3-(6-methoxy- pyridin-3-yl)-propionic acid300 3-Benzo[1,3]dioxol-4-yl-3-{[1-(3-fluoro- 414.16 3.07 LC3 Bphenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid 3013-(3-Chloro-phenyl)-3-{[1-(3-fluoro-phenyl)- 404.13 3.24 LC3 B5-hydroxy-1H-pyrazole-3-carbonyl]-amino}- propionic acid 302(S)-3-(2-Bromo-phenyl)-3-{[1-(3-fluoro- 448.08 3.17 LC3 Bphenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid 303(S)-3-(3-Cyano-phenyl)-3-{[1-(3-fluoro- 395.16 3.02 LC3 Cphenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid 3043-{[1-(3-Fluoro-phenyl)-5-hydroxy-1H- 438.15 3.29 LC3 Bpyrazole-3-carbonyl]-amino}-3-(3- trifluoromethyl-phenyl)-propionic acid305 (S)-3-(4-Cyano-phenyl)-3-{[1-(3-fluoro- 395.17 2.97 LC3 Bphenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid 3063-(2,4-Dimethoxy-phenyl)-3-{[1-(3-fluoro- 430.19 3.14 LC3 Bphenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid 307(S)-3-{[1-(3-Fluoro-phenyl)-5-hydroxy-1H- 400.18 3.12 LC3 Bpyrazole-3-carbonyl]-amino}-3-(2-methoxy- phenyl)-propionic acid 3083-(2-Fluoro-phenyl)-3-{[1-(3-fluoro-phenyl)- 388.15 3.05 LC3 B5-hydroxy-1H-pyrazole-3-carbonyl]-amino}- propionic acid 3093-(5-Chloro-2-methoxy-phenyl)-3-{[1-(3- 434.15 3.32 LC3 Bfluoro-phenyl)-5-hydroxy-1H-pyrazole-3- carbonyl]-amino}-propionic acid310 3-(2-Chloro-4-methoxy-phenyl)-3-{[1-(3- 434.17 3.18 LC3 Bfluoro-phenyl)-5-hydroxy-1H-pyrazole-3- carbonyl]-amino}-propionic acid311 (S)-3-(4-Fluoro-phenyl)-3-{[1-(3-fluoro- 388.16 3.10 LC3 Bphenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid 312(S)-3-(3-Fluoro-phenyl)-3-{[1-(3-fluoro- 388.16 3.10 LC3 Bphenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid 313(S)-3-{[1-(3-Fluoro-phenyl)-5-hydroxy-1H- 438.15 3.34 LC3 Cpyrazole-3-carbonyl]-amino}-3-(4- trifluoromethyl-phenyl)-propionic acid314 3-(2,3-Dichloro-phenyl)-3-{[1-(3-fluoro- 438.1 3.30 LC3 Aphenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid 3153-{[1-(3-Fluoro-phenyl)-5-hydroxy-1H- 454.16 3.43 LC3 Bpyrazole-3-carbonyl]-amino}-3-(4- trifluoromethoxy-phenyl)-propionicacid 316 (2R,3R)-3-{[1-(3-Fluoro-phenyl)-5-hydroxy- 416.18 2.89 LC3 C1H-pyrazole-3-carbonyl]-amino}-2-hydroxy- 3-(2-methoxy-phenyl)-propionicacid 317 (S)-3-{[1-(3-Fluoro-phenyl)-5-hydroxy-1H- 384.19 3.17 LC3 Bpyrazole-3-carbonyl]-amino}-3-m-tolyl- propionic acid 318(S)-3-{[1-(3-Fluoro-phenyl)-5-hydroxy-1H- 438.15 3.32 LC3 Bpyrazole-3-carbonyl]-amino}-3-(3- trifluoromethyl-phenyl)-propionic acid319 3-(3′-Fluoro-biphenyl-4-yl)-3-{[1-(3-fluoro- 464.22 3.52 LC3 Bphenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid 3203-(4-Chloro-2-fluoro-phenyl)-3-{[1-(3-fluoro- 422.13 3.29 LC3 Bphenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid 3213-(2,5-Dimethyl-phenyl)-3-{[1-(3-fluoro- 398.21 3.25 LC3 Bphenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid 3223-(3-Chloro-2-fluoro-phenyl)-3-{[1-(3-fluoro- 422.13 3.29 LC3 Bphenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid 3233-(2-Chloro-3-trifluoromethyl-phenyl)-3-{[1- 472.12 3.39 LC3 B(3-fluoro-phenyl)-5-hydroxy-1H-pyrazole-3- carbonyl]-amino}-propionicacid 324 3-(4-Ethyl-phenyl)-3-{[1-(3-fluoro-phenyl)-5- 398.2 3.32 LC3 Bhydroxy-1H-pyrazole-3-carbonyl]-amino}- propionic acid 3253-(2,4-Dimethyl-phenyl)-3-{[1-(3-fluoro- 398.2 3.27 LC3 Bphenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid 3263-(4-Fluoro-2-methyl-phenyl)-3-{[1-(3-fluoro- 402.18 3.24 LC3 Bphenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid 3273-Biphenyl-4-yl-3-{[1-(3-fluoro-phenyl)-5- 446.23 3.42 LC3 Bhydroxy-1H-pyrazole-3-carbonyl]-amino}- propionic acid 3283-(3,4-Dichloro-phenyl)-3-{[1-(3-fluoro- 438.11 3.39 LC3 Bphenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid 329(S)-3-{[1-(3-Fluoro-phenyl)-5-hydroxy-1H- 438.15 3.25 LC3 Bpyrazole-3-carbonyl]-amino}-3-(2- trifluoromethyl-phenyl)-propionic acid330 3-{[1-(3-Fluoro-phenyl)-5-hydroxy-1H- 462.21 3.49 LC3 Bpyrazole-3-carbonyl]-amino}-3-(4-phenoxy- phenyl)-propionic acid 331(S)-3-(4-Chloro-phenyl)-3-{[1-(3-fluoro- 404.14 3.24 LC3 Bphenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid 332(S)-3-(2,4-Dichloro-phenyl)-3-{[1-(3-fluoro- 438.1 3.35 LC3 Bphenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid 3333-(4′-Fluoro-biphenyl-4-yl)-3-{[1-(3-fluoro- 464.23 3.49 LC3 Cphenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid 334(S)-3-{[1-(3-Fluoro-phenyl)-5-hydroxy-1H- 371.17 2.29 LC3 Bpyrazole-3-carbonyl]-amino}-3-pyridin-3-yl- propionic acid 335(S)-3-{[1-(3-Fluoro-phenyl)-5-hydroxy-1H- 401.17 2.72 LC3 Bpyrazole-3-carbonyl]-amino}-3-(6-methoxy- pyridin-3-yl)-propionic acid336 3-Benzo[1,3]dioxol-4-yl-3-{[1-(4-fluoro- 414.17 3.04 LC3 Bphenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid 3373-{[1-(4-Fluoro-phenyl)-5-hydroxy-1H- 414.21 3.10 LC3 Bpyrazole-3-carbonyl]-amino}-3-(4-methoxy- 2-methyl-phenyl)-propionicacid 338 3-(3-Chloro-phenyl)-3-{[1-(4-fluoro-phenyl)- 404.13 3.17 LC3 B5-hydroxy-1H-pyrazole-3-carbonyl]-amino}- propionic acid 339(S)-3-(2-Bromo-phenyl)-3-{[1-(4-fluoro- 448.09 3.18 LC3 Bphenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid 340(S)-3-(3-Cyano-phenyl)-3-{[1-(4-fluoro- 395.17 2.93 LC3 Cphenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid 341(S)-3-(4-Cyano-phenyl)-3-{[1-(4-fluoro- 395.17 2.93 LC3 Bphenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid 342(S)-3-{[1-(4-Fluoro-phenyl)-5-hydroxy-1H- 400.19 3.07 LC3 Bpyrazole-3-carbonyl]-amino}-3-(2-methoxy- phenyl)-propionic acid 3433-(2-Fluoro-phenyl)-3-{[1-(4-fluoro-phenyl)- 388.16 3.07 LC3 C5-hydroxy-1H-pyrazole-3-carbonyl]-amino}- propionic acid 3443-(5-Chloro-2-methoxy-phenyl)-3-{[1-(4- 434.15 3.24 LC3 Bfluoro-phenyl)-5-hydroxy-1H-pyrazole-3- carbonyl]-amino}-propionic acid345 3-(2-Chloro-4-methoxy-phenyl)-3-{[1-(4- 434.17 3.20 LC3 Bfluoro-phenyl)-5-hydroxy-1H-pyrazole-3- carbonyl]-amino}-propionic acid346 (S)-3-(4-Fluoro-phenyl)-3-{[1-(4-fluoro- 388.16 3.10 LC3 Cphenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid 347(S)-3-(2,3-Dichloro-phenyl)-3-{[1-(4-fluoro- 438.1 3.27 LC3 Bphenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid 348(S)-3-{[1-(4-Fluoro-phenyl)-5-hydroxy-1H- 400.19 3.02 LC3 Cpyrazole-3-carbonyl]-amino}-3-(3-methoxy- phenyl)-propionic acid 349(S)-3-(3-Fluoro-phenyl)-3-{[1-(4-fluoro- 388.16 3.07 LC3 Bphenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid 350(S)-3-(3-Chloro-phenyl)-3-{[1-(4-fluoro- 404.14 3.18 LC3 Bphenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid 351(S)-3-{[1-(4-Fluoro-phenyl)-5-hydroxy-1H- 438.15 3.34 LC3 Cpyrazole-3-carbonyl]-amino}-3-(4- trifluoromethyl-phenyl)-propionic acid352 3-(2,3-Dichloro-phenyl)-3-{[1-(4-fluoro- 438.11 3.27 LC3 Bphenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid 353(S)-3-(2,3-Dimethoxy-phenyl)-3-{[1-(4-fluoro- 430.2 3.05 LC3 Bphenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid 354(S)-3-{[1-(4-Fluoro-phenyl)-5-hydroxy-1H- 384.19 3.14 LC3 Bpyrazole-3-carbonyl]-amino}-3-m-tolyl- propionic acid 355(S)-3-{[1-(4-Fluoro-phenyl)-5-hydroxy-1H- 438.16 3.29 LC3 Bpyrazole-3-carbonyl]-amino}-3-(3- trifluoromethyl-phenyl)-propionic acid356 3-(3′-Fluoro-biphenyl-4-yl)-3-{[1-(4-fluoro- 464.21 3.47 LC3 Bphenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid 3573-(4-Chloro-2-fluoro-phenyl)-3-{[1-(4-fluoro- 422.13 3.22 LC3 Bphenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid 3583-(2,3-Dimethyl-phenyl)-3-{[1-(4-fluoro- 398.21 3.22 LC3 Bphenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid 3593-(2,5-Dimethyl-phenyl)-3-{[1-(4-fluoro- 398.21 3.27 LC3 Cphenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid 3603-{[1-(4-Fluoro-phenyl)-5-hydroxy-1H- 456.16 3.35 LC3 Bpyrazole-3-carbonyl]-amino}-3-(2-fluoro-3-trifluoromethyl-phenyl)-propionic acid 3613-(3-Chloro-2-fluoro-phenyl)-3-{[1-(4-fluoro- 422.13 3.20 LC3 Bphenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid 3623-(2-Chloro-3-trifluoromethyl-phenyl)-3-{[1- 472.13 3.35 LC3 B(4-fluoro-phenyl)-5-hydroxy-1H-pyrazole-3- carbonyl]-amino}-propionicacid 363 3-(4-Ethyl-phenyl)-3-{[1-(4-fluoro-phenyl)-5- 398.2 3.27 LC3 Bhydroxy-1H-pyrazole-3-carbonyl]-amino}- propionic acid 3643-(4-Fluoro-2-methyl-phenyl)-3-{[1-(4-fluoro- 402.19 3.17 LC3 Bphenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid 3653-Biphenyl-4-yl-3-{[1-(4-fluoro-phenyl)-5- 446.22 3.42 LC3 Bhydroxy-1H-pyrazole-3-carbonyl]-amino}- propionic acid 366(S)-3-(2-Fluoro-phenyl)-3-{[1-(4-fluoro- 388.16 3.04 LC3 Bphenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid 367(S)-3-{[1-(4-Fluoro-phenyl)-5-hydroxy-1H- 438.16 3.22 LC3 Bpyrazole-3-carbonyl]-amino}-3-(2- trifluoromethyl-phenyl)-propionic acid368 (S)-3-(2,6-Difluoro-phenyl)-3-{[1-(4-fluoro- 406.15 3.07 LC3 Bphenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid 369(S)-3-(4-Chloro-phenyl)-3-{[1-(4-fluoro- 404.14 3.18 LC3 Bphenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid 370(S)-3-(2,4-Dichloro-phenyl)-3-{[1-(4-fluoro- 438.11 3.39 LC3 Bphenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid 3713-(4′-Fluoro-biphenyl-4-yl)-3-{[1-(4-fluoro- 464.22 3.47 LC3 Bphenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid 372(S)-3-{[1-(4-Fluoro-phenyl)-5-hydroxy-1H- 371.17 2.22 LC3 Cpyrazole-3-carbonyl]-amino}-3-pyridin-3-yl- propionic acid 3733-[(5-Hydroxy-1-phenyl-1H-pyrazole-3- 396.22 3.05 LC3 Bcarbonyl)-amino]-3-(4-methoxy-2-methyl- phenyl)-propionic acid 374(S)-3-[(5-Hydroxy-1-phenyl-1H-pyrazole-3- 382.21 2.93 LC3 Bcarbonyl)-amino]-3-(4-methoxy-phenyl)- propionic acid 3753-(5-Chloro-2-methoxy-phenyl)-3-[(5- 416.16 3.24 LC3 Bhydroxy-1-phenyl-1H-pyrazole-3-carbonyl)- amino]-propionic acid 376(S)-3-[(5-Hydroxy-1-phenyl-1H-pyrazole-3- 366.19 3.07 LC3 Bcarbonyl)-amino]-3-m-tolyl-propionic acid 3773-(2,3-Dimethyl-phenyl)-3-[(5-hydroxy-1- 380.21 3.15 LC3 Bphenyl-1H-pyrazole-3-carbonyl)-amino]- propionic acid 3783-(2,5-Dimethyl-phenyl)-3-[(5-hydroxy-1- 380.21 3.22 LC3 Bphenyl-1H-pyrazole-3-carbonyl)-amino]- propionic acid 3793-{[1-(2,4-Difluoro-phenyl)-5-hydroxy-1H- 432.22 2.99 LC3 Bpyrazole-3-carbonyl]-amino}-3-(4-methoxy- 2-methyl-phenyl)-propionicacid 380 3-(3-Chloro-phenyl)-3-{[1-(2,4-difluoro- 422.15 3.14 LC3 Bphenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid 381(S)-3-(3-Cyano-phenyl)-3-{[1-(2,4-difluoro- 413.17 2.87 LC3 Bphenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid 382(S)-3-{[1-(2,4-Difluoro-phenyl)-5-hydroxy- 418.19 2.93 LC3 B1H-pyrazole-3-carbonyl]-amino}-3-(4- methoxy-phenyl)-propionic acid 3833-{[1-(2,4-Difluoro-phenyl)-5-hydroxy-1H- 448.21 3.00 LC3 Bpyrazole-3-carbonyl]-amino}-3-(2,4- dimethoxy-phenyl)-propionic acid 3843-{[1-(2,4-Difluoro-phenyl)-5-hydroxy-1H- 482.21 3.42 LC3 Bpyrazole-3-carbonyl]-amino}-3-(3′-fluoro- biphenyl-4-yl)-propionic acid385 3-{[1-(2,4-Difluoro-phenyl)-5-hydroxy-1H- 474.17 3.25 LC3 Apyrazole-3-carbonyl]-amino}-3-(2-fluoro-3-trifluoromethyl-phenyl)-propionic acid 3863-[3-(4-Chloro-phenoxy)-phenyl]-3-{[1-(2,4- 514.16 3.60 LC3 Bdifluoro-phenyl)-5-hydroxy-1H-pyrazole-3- carbonyl]-amino}-propionicacid 387 (S)-3-{[1-(2,4-Difluoro-phenyl)-5-hydroxy- 406.15 2.97 LC3 B1H-pyrazole-3-carbonyl]-amino}-3-(2-fluoro- phenyl)-propionic acid 388(S)-3-(2,6-Difluoro-phenyl)-3-{[1-(2,4- 424.15 3.02 LC3 Bdifluoro-phenyl)-5-hydroxy-1H-pyrazole-3- carbonyl]-amino}-propionicacid 389 (S)-3-{[1-(2,4-Difluoro-phenyl)-5-hydroxy- 389.18 2.12 LC3 C1H-pyrazole-3-carbonyl]-amino}-3-pyridin-3- yl-propionic acid 390(S)-3-{[1-(2,4-Difluoro-phenyl)-5-hydroxy- 419.19 2.60 LC3 B1H-pyrazole-3-carbonyl]-amino}-3-(6- methoxy-pyridin-3-yl)-propionicacid 391 3-(3-Chloro-phenyl)-3-{[1-(2-chloro-phenyl)- 420.1 3.12 LC3 B5-hydroxy-1H-pyrazole-3-carbonyl]-amino}- propionic acid 392(S)-3-{[1-(2-Chloro-phenyl)-5-hydroxy-1H- 416.17 2.90 LC3 Bpyrazole-3-carbonyl]-amino}-3-(4-methoxy- phenyl)-propionic acid 393(S)-3-{[1-(2-Chloro-phenyl)-5-hydroxy-1H- 404.13 2.99 LC3 Bpyrazole-3-carbonyl]-amino}-3-(3-fluoro- phenyl)-propionic acid 394(S)-3-{[1-(2-Chloro-phenyl)-5-hydroxy-1H- 446.17 2.97 LC3 Bpyrazole-3-carbonyl]-amino}-3-(2,3- dimethoxy-phenyl)-propionic acid 3953-{[1-(2-Fluoro-phenyl)-5-hydroxy-1H- 414.21 2.93 LC3 Bpyrazole-3-carbonyl]-amino}-3-(4-methoxy- 2-methyl-phenyl)-propionicacid 396 3-(3-Chloro-phenyl)-3-{[1-(2-fluoro-phenyl)- 404.13 3.04 LC3 B5-hydroxy-1H-pyrazole-3-carbonyl]-amino}- propionic acid 397(S)-3-(2-Bromo-phenyl)-3-{[1-(2-fluoro- 448.08 3.05 LC3 Aphenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid 398(S)-3-{[1-(2-Fluoro-phenyl)-5-hydroxy-1H- 400.18 2.89 LC3 Bpyrazole-3-carbonyl]-amino}-3-(4-methoxy- phenyl)-propionic acid 399(S)-3-(2,3-Dichloro-phenyl)-3-{[1-(2-fluoro- 438.09 3.18 LC3 Aphenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid 400(S)-3-(3-Fluoro-phenyl)-3-{[1-(2-fluoro- 388.16 2.90 LC3 Bphenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid 401(S)-3-(3-Chloro-phenyl)-3-{[1-(2-fluoro- 404.12 3.02 LC3 Bphenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid 4023-(2,3-Dichloro-phenyl)-3-{[1-(2-fluoro- 438.09 3.15 LC3 Aphenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid 403(S)-3-(2,3-Dimethoxy-phenyl)-3-{[1-(2-fluoro- 430.19 2.93 LC3 Bphenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid 404(S)-3-{[1-(2-Fluoro-phenyl)-5-hydroxy-1H- 384.17 2.95 LC3 Bpyrazole-3-carbonyl]-amino}-3-m-tolyl- propionic acid 4053-(2,3-Dimethyl-phenyl)-3-{[1-(2-fluoro- 398.21 3.07 LC3 Aphenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid 4063-(2,5-Dimethyl-phenyl)-3-{[1-(2-fluoro- 398.2 3.14 LC3 Bphenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid 4073-(3,4-Dichloro-phenyl)-3-{[1-(2-fluoro- 438.09 3.17 LC3 Bphenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid 4083-(3-Chloro-phenyl)-3-{[1-(3-chloro-phenyl)- 420.11 3.37 LC3 B5-hydroxy-1H-pyrazole-3-carbonyl]-amino}- propionic acid 409(S)-3-{[1-(3-Chloro-phenyl)-5-hydroxy-1H- 416.16 3.14 LC3 Cpyrazole-3-carbonyl]-amino}-3-(4-methoxy- phenyl)-propionic acid 410(S)-3-{[1-(3-Chloro-phenyl)-5-hydroxy-1H- 411.15 3.15 LC3 Cpyrazole-3-carbonyl]-amino}-3-(4-cyano- phenyl)-propionic acid 411(S)-3-{[1-(3-Chloro-phenyl)-5-hydroxy-1H- 404.14 3.22 LC3 Cpyrazole-3-carbonyl]-amino}-3-(4-fluoro- phenyl)-propionic acid 412(S)-3-{[1-(3-Chloro-phenyl)-5-hydroxy-1H- 454.08 3.42 LC3 Cpyrazole-3-carbonyl]-amino}-3-(2,3-dichloro- phenyl)-propionic acid 413(S)-3-{[1-(3-Chloro-phenyl)-5-hydroxy-1H- 416.16 3.22 LC3 Cpyrazole-3-carbonyl]-amino}-3-(3-methoxy- phenyl)-propionic acid 414(S)-3-{[1-(3-Chloro-phenyl)-5-hydroxy-1H- 404.14 3.20 LC3 Cpyrazole-3-carbonyl]-amino}-3-(3-fluoro- phenyl)-propionic acid 415(S)-3-(3-Chloro-phenyl)-3-{[1-(3-chloro- 420.11 3.39 LC3 Bphenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid 416(2R,3R)-3-{[1-(3-Chloro-phenyl)-5-hydroxy- 432.15 3.02 LC3 C1H-pyrazole-3-carbonyl]-amino}-2-hydroxy- 3-(2-methoxy-phenyl)-propionicacid 417 (S)-3-{[1-(3-Chloro-phenyl)-5-hydroxy-1H- 446.17 3.25 LC3 Bpyrazole-3-carbonyl]-amino}-3-(2,3- dimethoxy-phenyl)-propionic acid 4183-{[1-(3-Chloro-phenyl)-5-hydroxy-1H- 472.15 3.45 LC3 Cpyrazole-3-carbonyl]-amino}-3-(2-fluoro-3-trifluoromethyl-phenyl)-propionic acid 4193-{[1-(3-Chloro-phenyl)-5-hydroxy-1H- 414.19 3.39 LC3 Bpyrazole-3-carbonyl]-amino}-3-(2,4-dimethyl- phenyl)-propionic acid 4203-{[1-(3-Chloro-phenyl)-5-hydroxy-1H- 418.16 3.35 LC3 Bpyrazole-3-carbonyl]-amino}-3-(4-fluoro-2- methyl-phenyl)-propionic acid421 3-Biphenyl-4-yl-3-{[1-(3-chloro-phenyl)-5- 462.2 3.59 LC3 Bhydroxy-1H-pyrazole-3-carbonyl]-amino}- propionic acid 422(S)-3-{[1-(3-Chloro-phenyl)-5-hydroxy-1H- 404.12 3.18 LC3 Bpyrazole-3-carbonyl]-amino}-3-(2-fluoro- phenyl)-propionic acid 423(S)-3-{[1-(4-Chloro-phenyl)-5-hydroxy-1H- 416.15 3.22 LC3 Cpyrazole-3-carbonyl]-amino}-3-(4-methoxy- phenyl)-propionic acid 4243-(2-Chloro-4-methoxy-phenyl)-3-{[1-(4- 450.14 3.37 LC3 Bchloro-phenyl)-5-hydroxy-1H-pyrazole-3- carbonyl]-amino}-propionic acid425 3-{[1-(4-Chloro-phenyl)-5-hydroxy-1H- 480.2 3.68 LC3 Cpyrazole-3-carbonyl]-amino}-3-(4′-fluoro- biphenyl-4-yl)-propionic acid426 3-{[1-(3-Fluoro-phenyl)-5-hydroxy-1H- 414.2 3.12 LC3 Bpyrazole-3-carbonyl]-amino}-3-(4-methoxy- 2-methyl-phenyl)-propionicacid 427 (S)-3-{[1-(3-Fluoro-phenyl)-5-hydroxy-1H- 400.19 3.07 LC3 Cpyrazole-3-carbonyl]-amino}-3-(4-methoxy- phenyl)-propionic acid 428(S)-3-(2,3-Dichloro-phenyl)-3-{[1-(3-fluoro- 438.1 3.37 LC3 Bphenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid 429(S)-3-{[1-(3-Fluoro-phenyl)-5-hydroxy-1H- 400.18 3.05 LC3 Bpyrazole-3-carbonyl]-amino}-3-(3-methoxy- phenyl)-propionic acid 430(S)-3-(3-Chloro-phenyl)-3-{[1-(3-fluoro- 404.13 3.24 LC3 Bphenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid 431(S)-3-(2,3-Dimethoxy-phenyl)-3-{[1-(3-fluoro- 430.2 3.09 LC3 Bphenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid 4323-(2,3-Dimethyl-phenyl)-3-{[1-(3-fluoro- 398.21 3.30 LC3 Bphenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid 433(S)-3-(2-Fluoro-phenyl)-3-{[1-(3-fluoro- 388.16 3.12 LC3 Bphenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid 434(S)-3-(2,6-Difluoro-phenyl)-3-{[1-(3-fluoro- 406.15 3.10 LC3 Bphenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid 435(S)-3-{[1-(4-Fluoro-phenyl)-5-hydroxy-1H- 400.2 2.99 LC3 Bpyrazole-3-carbonyl]-amino}-3-(4-methoxy- phenyl)-propionic acid 4363-(2,4-Dimethoxy-phenyl)-3-{[1-(4-fluoro- 430.21 3.09 LC3 Cphenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid 4373-{[1-(4-Fluoro-phenyl)-5-hydroxy-1H- 462.22 3.47 LC3 Bpyrazole-3-carbonyl]-amino}-3-(4-phenoxy- phenyl)-propionic acid 438(S)-3-{[1-(4-Fluoro-phenyl)-5-hydroxy-1H- 401.18 2.70 LC3 Bpyrazole-3-carbonyl]-amino}-3-(6-methoxy- pyridin-3-yl)-propionic acid439 3-Biphenyl-4-yl-3-{[1-(2-chloro-pyridin-4-yl)- 463.13 3.06 LC8 B5-hydroxy-1H-pyrazole-3-carbonyl]-amino}- propionic acid 4403-Biphenyl-4-yl-3-[(5-hydroxy-1-pyridin-3-yl- 429.17 2.66 LC8 C1H-pyrazole-3-carbonyl)-amino]-propionic acid 4413-(2-Fluoro-6-methoxy-phenyl)-3-[(5- 400.19 3.04 LC3 Bhydroxy-1-phenyl-1H-pyrazole-3-carbonyl)- amino]-propionic acid 4423-[(5-Hydroxy-1-phenyl-1H-pyrazole-3- 444.23 3.42 LC3 Ccarbonyl)-amino]-3-(2-phenoxy-phenyl)- propionic acid 4433-(5-Fluoro-2-trifluoromethyl-phenyl)-3-[(5- 438.14 3.25 LC3 Bhydroxy-1-phenyl-1H-pyrazole-3-carbonyl)- amino]-propionic acid 4443-(2,5-Dichloro-phenyl)-3-[(5-hydroxy-1- 420.11 3.22 LC3 Aphenyl-1H-pyrazole-3-carbonyl)-amino]- propionic acid 445(S)-3-[(5-Hydroxy-1-phenyl-1H-pyrazole-3- 366.2 3.09 LC3 Bcarbonyl)-amino]-3-p-tolyl-propionic acid 446(S)-3-(2-Chloro-phenyl)-3-[(5-hydroxy-1- 386.15 3.02 LC3 Bphenyl-1H-pyrazole-3-carbonyl)-amino]- propionic acid 4473-{[1-(2,4-Difluoro-phenyl)-5-hydroxy-1H- 420.18 3.07 LC3 Bpyrazole-3-carbonyl]-amino}-3-(3-fluoro-2- methyl-phenyl)-propionic acid448 3-(2-Chloro-4-dimethylamino-phenyl)-3-{[1- 465.2 2.89 LC3 B(2,4-difluoro-phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]-amino}-propionic acid 4493-{[1-(2,4-Difluoro-phenyl)-5-hydroxy-1H- 436.19 3.04 LC3 Bpyrazole-3-carbonyl]-amino}-3-(2-fluoro-6- methoxy-phenyl)-propionicacid 450 3-(2,2-Difluoro-benzo[1,3]dioxol-4-yl)-3-{[1- 468.14 3.20 LC3 B(2,4-difluoro-phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]-amino}-propionic acid 4513-(2,5-Difluoro-phenyl)-3-{[1-(2,4-difluoro- 424.16 2.99 LC3 Bphenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid 4523-{[1-(2,4-Difluoro-phenyl)-5-hydroxy-1H- 474.14 3.37 LC3 Bpyrazole-3-carbonyl]-amino}-3-(5-fluoro-2-trifluoromethyl-phenyl)-propionic acid 4533-{[1-(2,4-Difluoro-phenyl)-5-hydroxy-1H- 436.17 3.04 LC3 Bpyrazole-3-carbonyl]-amino}-3-(5-fluoro-2- methoxy-phenyl)-propionicacid 454 (S)-3-{[1-(2,4-Difluoro-phenyl)-5-hydroxy- 402.18 3.04 LC3 B1H-pyrazole-3-carbonyl]-amino}-3-p-tolyl- propionic acid 4553-{[1-(2-Chloro-phenyl)-5-hydroxy-1H- 418.15 3.04 LC3 Bpyrazole-3-carbonyl]-amino}-3-(3-fluoro-2- methyl-phenyl)-propionic acid456 3-(2-Chloro-4-dimethylamino-phenyl)-3-{[1- 463.17 2.90 LC3 C(2-chloro-phenyl)-5-hydroxy-1H-pyrazole-3- carbonyl]-amino}-propionicacid; compound with trifluoro-acetic acid 4573-{[1-(2-Chloro-phenyl)-5-hydroxy-1H- 434.17 3.02 LC3 Bpyrazole-3-carbonyl]-amino}-3-(2-fluoro-6- methoxy-phenyl)-propionicacid 458 3-(2-Chloro-5-fluoro-phenyl)-3-{[1-(2-chloro- 438.1 3.09 LC3 Bphenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid 4593-{[1-(2-Chloro-phenyl)-5-hydroxy-1H- 422.15 2.97 LC3 Bpyrazole-3-carbonyl]-amino}-3-(2,5-difluoro- phenyl)-propionic acid 4603-{[1-(2-Chloro-phenyl)-5-hydroxy-1H- 472.16 3.18 LC3 Bpyrazole-3-carbonyl]-amino}-3-(5-fluoro-2-trifluoromethyl-phenyl)-propionic acid 4613-{[1-(2-Chloro-phenyl)-5-hydroxy-1H- 418.16 3.10 LC3 Bpyrazole-3-carbonyl]-amino}-3-(5-fluoro-2- methyl-phenyl)-propionic acid462 3-{[1-(2-Chloro-phenyl)-5-hydroxy-1H- 454.1 3.17 LC3 Apyrazole-3-carbonyl]-amino}-3-(2,5-dichloro- phenyl)-propionic acid 4633-(2-Chloro-4-dimethylamino-phenyl)-3-{[1- 461.24 4.39 LC4 C(3-chloro-phenyl)-5-hydroxy-1H-pyrazole-3- [(M − H)⁻]carbonyl]-amino}-propionic acid 4643-{[1-(3-Chloro-phenyl)-5-hydroxy-1H- 466.14 3.40 LC3 Bpyrazole-3-carbonyl]-amino}-3-(2,2-difluoro-benzo[1,3]dioxol-4-yl)-propionic acid 4653-{[1-(3-Chloro-phenyl)-5-hydroxy-1H- 422.14 3.29 LC3 Bpyrazole-3-carbonyl]-amino}-3-(2,5-difluoro- phenyl)-propionic acid 4663-{[1-(3-Chloro-phenyl)-5-hydroxy-1H- 472.16 3.42 LC3 Bpyrazole-3-carbonyl]-amino}-3-(5-fluoro-2-trifluoromethyl-phenyl)-propionic acid 4673-{[1-(3-Chloro-phenyl)-5-hydroxy-1H- 486.13 3.50 LC3 Cpyrazole-3-carbonyl]-amino}-3-(2-trifluoromethylsulfanyl-phenyl)-propionic acid 4683-{[1-(4-Chloro-phenyl)-5-hydroxy-1H- 418.19 3.32 LC3 Bpyrazole-3-carbonyl]-amino}-3-(3-fluoro-2- methyl-phenyl)-propionic acid469 3-{[1-(4-Chloro-phenyl)-5-hydroxy-1H- 434.17 3.32 LC3 Bpyrazole-3-carbonyl]-amino}-3-(2-fluoro-6- methoxy-phenyl)-propionicacid 470 3-(2-Chloro-5-fluoro-phenyl)-3-{[1-(4-chloro- 438.11 3.32 LC3 Bphenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid 4713-{[1-(4-Chloro-phenyl)-5-hydroxy-1H- 466.13 3.40 LC3 Bpyrazole-3-carbonyl]-amino}-3-(2,2-difluoro-benzo[1,3]dioxol-4-yl)-propionic acid 4723-{[1-(4-Chloro-phenyl)-5-hydroxy-1H- 422.14 3.25 LC3 Cpyrazole-3-carbonyl]-amino}-3-(2,5-difluoro- phenyl)-propionic acid 4733-{[1-(4-Chloro-phenyl)-5-hydroxy-1H- 472.13 3.42 LC3 Cpyrazole-3-carbonyl]-amino}-3-(5-fluoro-2-trifluoromethyl-phenyl)-propionic acid 474(S)-3-(2-Chloro-phenyl)-3-{[1-(4-chloro- 420.12 3.27 LC3 Bphenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid 4753-(2-Chloro-5-fluoro-phenyl)-3-{[1-(2-fluoro- 422.15 3.00 LC3 Bphenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid 4763-(2,2-Difluoro-benzo[1,3]dioxol-4-yl)-3-{[1- 450.15 3.22 LC3 B(2-fluoro-phenyl)-5-hydroxy-1H-pyrazole-3- carbonyl]-amino}-propionicacid 477 3-{[1-(2-Fluoro-phenyl)-5-hydroxy-1H- 456.17 3.12 LC3 Bpyrazole-3-carbonyl]-amino}-3-(5-fluoro-2-trifluoromethyl-phenyl)-propionic acid 4783-(5-Fluoro-2-methyl-phenyl)-3-{[1-(2-fluoro- 402.19 3.02 LC3 Aphenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid 4793-(2,5-Dichloro-phenyl)-3-{[1-(2-fluoro- 438.12 3.14 LC3 Aphenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid 480(S)-3-{[1-(2-Fluoro-phenyl)-5-hydroxy-1H- 384.21 2.97 LC3 Bpyrazole-3-carbonyl]-amino}-3-p-tolyl- propionic acid 4813-{[1-(2-Fluoro-phenyl)-5-hydroxy-1H- 445.34 2.87 LC4 Bpyrazole-3-carbonyl]-amino}-3-(4-pyridin-2- [(M − H)⁻]yl-phenyl)-propionic acid 4823-(3-Fluoro-2-methyl-phenyl)-3-{[1-(3-fluoro- 402.2 3.18 LC3 Bphenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid 4833-(2-Chloro-5-fluoro-phenyl)-3-{[1-(3-fluoro- 422.14 3.22 LC3 Bphenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid 4843-(2,2-Difluoro-benzo[1,3]dioxol-4-yl)-3-{[1- 450.18 3.27 LC3 B(3-fluoro-phenyl)-5-hydroxy-1H-pyrazole-3- carbonyl]-amino}-propionicacid 485 3-(2,5-Difluoro-phenyl)-3-{[1-(3-fluoro- 406.17 3.10 LC3 Bphenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid 4863-{[1-(3-Fluoro-phenyl)-5-hydroxy-1H- 456.17 3.49 LC3 Bpyrazole-3-carbonyl]-amino}-3-(5-fluoro-2-trifluoromethyl-phenyl)-propionic acid 4873-(5-Fluoro-2-methyl-phenyl)-3-{[1-(3-fluoro- 402.19 3.18 LC3 Bphenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid 4883-(2,5-Dichloro-phenyl)-3-{[1-(3-fluoro- 438.12 3.32 LC3 Bphenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid 489(S)-3-{[1-(3-Fluoro-phenyl)-5-hydroxy-1H- 384.21 3.20 LC3 Bpyrazole-3-carbonyl]-amino}-3-p-tolyl- propionic acid 4903-(2-Chloro-4-dimethylamino-phenyl)-3-{[1- 447.22 2.95 LC3 C(4-fluoro-phenyl)-5-hydroxy-1H-pyrazole-3- carbonyl]-amino}-propionicacid 491 3-(2,2-Difluoro-benzo[1,3]dioxol-4-yl)-3-{[1- 450.16 3.24 LC3 B(4-fluoro-phenyl)-5-hydroxy-1H-pyrazole-3- carbonyl]-amino}-propionicacid 492 3-(5-Fluoro-2-methyl-phenyl)-3-{[1-(4-fluoro- 402.19 3.22 LC3 Bphenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid 4933-(2,5-Dichloro-phenyl)-3-{[1-(4-fluoro- 438.08 3.29 LC3 Bphenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid 4943-(3-Fluoro-2-methyl-phenyl)-3-[(5-hydroxy- 384.19 3.14 LC3 B1-phenyl-1H-pyrazole-3-carbonyl)-amino]- propionic acid 4953-(2-Chloro-5-fluoro-phenyl)-3-[(5-hydroxy- 404.13 3.12 LC3 B1-phenyl-1H-pyrazole-3-carbonyl)-amino]- propionic acid 4963-(2,2-Difluoro-benzo[1,3]dioxol-4-yl)-3-[(5- 432.14 3.20 LC3 Bhydroxy-1-phenyl-1H-pyrazole-3-carbonyl)- amino]-propionic acid 4973-(5-Fluoro-2-methyl-phenyl)-3-[(5-hydroxy- 384.2 3.09 LC3 B1-phenyl-1H-pyrazole-3-carbonyl)-amino]- propionic acid 4983-(5-Fluoro-2-methoxy-phenyl)-3-[(5- 400.18 3.10 LC3 Bhydroxy-1-phenyl-1H-pyrazole-3-carbonyl)- amino]-propionic acid 4993-[(5-Hydroxy-1-phenyl-1H-pyrazole-3- 429.22 2.39 LC3 Bcarbonyl)-amino]-3-(4-pyridin-2-yl-phenyl)- propionic acid; compoundwith trifluoro- acetic acid 5003-(2,5-Dichloro-phenyl)-3-{[1-(2,4-difluoro- 456.1 3.18 LC3 Aphenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid 5013-{[1-(2,4-Difluoro-phenyl)-5-hydroxy-1H- 465.21 2.40 LC3 Apyrazole-3-carbonyl]-amino}-3-(4-pyridin-2- yl-phenyl)-propionic acid;compound with trifluoro-acetic acid 502(S)-3-(2-Chloro-phenyl)-3-{[1-(2,4-difluoro- 422.12 3.14 LC3 Bphenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid 5033-{[1-(2-Chloro-phenyl)-5-hydroxy-1H- 466.11 3.17 LC3 Bpyrazole-3-carbonyl]-amino}-3-(2,2-difluoro-benzo[1,3]dioxol-4-yl)-propionic acid 5043-{[1-(2-Chloro-phenyl)-5-hydroxy-1H- 434.16 3.00 LC3 Bpyrazole-3-carbonyl]-amino}-3-(5-fluoro-2- methoxy-phenyl)-propionicacid 505 3-{[1-(2-Chloro-phenyl)-5-hydroxy-1H- 469.29 2.85 LC4 Cpyrazole-3-carbonyl]-amino}-3-(4-morpholin- [(M − H)⁻]4-yl-phenyl)-propionic acid 506 3-{[1-(2-Chloro-phenyl)-5-hydroxy-1H-463.21 2.39 LC3 A pyrazole-3-carbonyl]-amino}-3-(4-pyridin-2-yl-phenyl)-propionic acid 507 (S)-3-(2-Chloro-phenyl)-3-{[1-(2-chloro-420.12 3.17 LC3 B phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]-amino}-propionic acid 508 3-{[1-(3-Chloro-phenyl)-5-hydroxy-1H- 418.173.32 LC3 B pyrazole-3-carbonyl]-amino}-3-(3-fluoro-2-methyl-phenyl)-propionic acid 5093-(2-Chloro-5-fluoro-phenyl)-3-{[1-(3-chloro- 438.12 3.34 LC3 Bphenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid 5103-{[1-(3-Chloro-phenyl)-5-hydroxy-1H- 418.17 3.32 LC3 Bpyrazole-3-carbonyl]-amino}-3-(5-fluoro-2- methyl-phenyl)-propionic acid511 3-{[1-(3-Chloro-phenyl)-5-hydroxy-1H- 454.05 4.47 LC4 Bpyrazole-3-carbonyl]-amino}-3-(2,5-dichloro- [(M − H)⁻]phenyl)-propionic acid 512 (S)-3-{[1-(3-Chloro-phenyl)-5-hydroxy-1H-400.18 3.30 LC3 B pyrazole-3-carbonyl]-amino}-3-p-tolyl- propionic acid513 3-{[1-(3-Chloro-phenyl)-5-hydroxy-1H- 463.2 2.59 LC3 Bpyrazole-3-carbonyl]-amino}-3-(4-pyridin-2- yl-phenyl)-propionic acid514 (S)-3-(2-Chloro-phenyl)-3-{[1-(3-chloro- 420.13 3.32 LC3 Bphenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid 5153-{[1-(4-Chloro-phenyl)-5-hydroxy-1H- 463.19 2.59 LC3 Bpyrazole-3-carbonyl]-amino}-3-(4-pyridin-2- yl-phenyl)-propionic acid516 3-(3-Fluoro-2-methyl-phenyl)-3-{[1-(2-fluoro- 402.19 3.00 LC3 Bphenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid 5173-(2,5-Difluoro-phenyl)-3-{[1-(2-fluoro- 406.16 2.90 LC3 Bphenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid 5183-{[1-(2-Fluoro-phenyl)-5-hydroxy-1H- 453.32 3.26 LC4 Cpyrazole-3-carbonyl]-amino}-3-(4-morpholin- [(M − H)⁻]4-yl-phenyl)-propionic acid 519 (S)-3-(2-Chloro-phenyl)-3-{[1-(2-fluoro-404.14 2.95 LC3 B phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]-amino}-propionic acid 520 3-(5-Fluoro-2-methoxy-phenyl)-3-{[1-(3- 418.193.17 LC3 B fluoro-phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]-amino}-propionic acid 5213-{[1-(3-Fluoro-phenyl)-5-hydroxy-1H- 447.24 2.50 LC3 Bpyrazole-3-carbonyl]-amino}-3-(4-pyridin-2- yl-phenyl)-propionic acid522 (S)-3-(2-Chloro-phenyl)-3-{[1-(3-fluoro- 404.15 3.32 LC3 Bphenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid 5233-(3-Fluoro-2-methyl-phenyl)-3-{[1-(4-fluoro- 402.2 3.17 LC3 Bphenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid 5243-(2-Chloro-5-fluoro-phenyl)-3-{[1-(4-fluoro- 422.14 3.20 LC3 Bphenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid 5253-(5-Fluoro-2-methoxy-phenyl)-3-{[1-(4- 418.16 3.17 LC3 Cfluoro-phenyl)-5-hydroxy-1H-pyrazole-3- carbonyl]-amino}-propionic acid526 (S)-3-{[1-(4-Fluoro-phenyl)-5-hydroxy-1H- 384.17 3.15 LC3 Bpyrazole-3-carbonyl]-amino}-3-p-tolyl- propionic acid 5273-{[1-(4-Fluoro-phenyl)-5-hydroxy-1H- 447.19 2.45 LC3 Bpyrazole-3-carbonyl]-amino}-3-(4-pyridin-2- yl-phenyl)-propionic acid528 (S)-3-(2-Chloro-phenyl)-3-{[1-(4-fluoro- 404.11 3.10 LC3 Bphenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid 5292,2-Dimethyl-propionic acid (S)-3-{[1-(2- 498.21 3.65 LC3fluoro-phenyl)-5-hydroxy-1H-pyrazole-3- carbonyl]-amino}-3-o-tolyl-propionyloxymethyl ester 530 (R)-3-{[1-(2-Fluoro-phenyl)-5-hydroxy-1H-398.17 3.32 LC3 pyrazole-3-carbonyl]-amino}-3-phenyl- butyric acidmethyl ester 531 3-{[1-(2-Fluoro-phenyl)-5-hydroxy-1H- 477.13 2.99 LC8 Bpyrazole-3-carbonyl]-amino}-3-[4-(6-methoxy-pyridin-3-yl)-phenyl]-propionic acid 532(S)-3-[(5-Hydroxy-1-o-tolyl-1H-pyrazole-3- 380.14 3.10 LC8 Acarbonyl)-amino]-3-o-tolyl-propionic acid 533(S)-3-[(1-Benzyl-5-hydroxy-1H-pyrazole-3- 380.14 3.07 LC8 Bcarbonyl)-amino]-3-o-tolyl-propionic acid 534(S)-3-[(5-Methoxy-1-phenyl-1H-pyrazole-3- 380.14 3.29 LC8 Acarbonyl)-amino]-3-o-tolyl-propionic acid 5353-{[1-(2-Fluoro-phenyl)-5-hydroxy-1H- 370.11 2.95 LC8 Bpyrazole-3-carbonyl]-amino}-3-phenyl- propionic acid 5363-(4′-Fluoro-biphenyl-4-yl)-3-[(5-hydroxy-1- 460.18 3.14 LC8 Ao-tolyl-1H-pyrazole-3-carbonyl)-amino]- propionic acid 537(S)-3-{[5-Hydroxy-1-(2-trifluoromethyl- 434.11 2.86 LC8 Bphenyl)-1H-pyrazole-3-carbonyl]-amino}-3-o- tolyl-propionic acid 5383-[(1-Benzyl-5-hydroxy-1H-pyrazole-3- 460.17 3.12 LC8 Bcarbonyl)-amino]-3-(4′-fluoro-biphenyl-4-yl)- propionic acid 5393-(2′-Chloro-biphenyl-4-yl)-3-[(5-hydroxy-1- 462.11 3.21 LC8 Bphenyl-1H-pyrazole-3-carbonyl)-amino]- propionic acid 5403-(3′-Chloro-biphenyl-4-yl)-3-{[1-(2-chloro- 496.08 3.25 LC8 Bphenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid 5413-(3′-Chloro-biphenyl-4-yl)-3-{[1-(2-fluoro- 480.11 3.21 LC8 Bphenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid 5423-(2′-Chloro-biphenyl-4-yl)-3-{[1-(2-fluoro- 480.1 3.14 LC8 Aphenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid 5433-(4′-Fluoro-biphenyl-4-yl)-3-{[1-(2-fluoro- 478.14 3.30 LC8 Bphenyl)-5-methoxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid 5443-(4′-Fluoro-biphenyl-4-yl)-3-[(5-methoxy-1- 460.15 3.37 LC8 Cphenyl-1H-pyrazole-3-carbonyl)-amino]- propionic acid 5453-[(5-Hydroxy-1-phenyl-1H-pyrazole-3- 458.12 3.20 LC8 Ccarbonyl)-amino]-3-(3-methoxy-biphenyl-4- yl)-propionic acid 5463-[(5-Hydroxy-1-phenyl-1H-pyrazole-3- 450.09 2.95 LC8 Bcarbonyl)-amino]-3-(4-methoxy-2- trifluoromethyl-phenyl)-propionic acid547 3-(2-Fluoro-5-methoxy-phenyl)-3-[(5- 400.1 2.80 LC8 Chydroxy-1-phenyl-1H-pyrazole-3-carbonyl)- amino]-propionic acid 5483-[(5-Hydroxy-1-phenyl-1H-pyrazole-3- 450.08 3.02 LC8 Ccarbonyl)-amino]-3-(2-methoxy-5- trifluoromethyl-phenyl)-propionic acid549 3-[(5-Hydroxy-1-phenyl-1H-pyrazole-3- 458.16 3.17 LC8 Ccarbonyl)-amino]-3-(4-methoxy-biphenyl-3- yl)-propionic acid 5503-{[1-(2-Fluoro-phenyl)-5-hydroxy-1H- 437.13 2.40 LC8 Bpyrazole-3-carbonyl]-amino}-3-(4- [1,2,4]triazol-1-yl-phenyl)-propionicacid 551 3-{[1-(2-Fluoro-phenyl)-5-hydroxy-1H- 476.15 3.12 LC8 Bpyrazole-3-carbonyl]-amino}-3-(3-methoxy- biphenyl-4-yl)-propionic acid552 3-{[1-(2-Fluoro-phenyl)-5-hydroxy-1H- 468.09 2.90 LC8 Bpyrazole-3-carbonyl]-amino}-3-(4-methoxy-2-trifluoromethyl-phenyl)-propionic acid 5533-(2-Fluoro-5-methoxy-phenyl)-3-{[1-(2- 418.09 2.74 LC8 Bfluoro-phenyl)-5-hydroxy-1H-pyrazole-3- carbonyl]-amino}-propionic acid554 3-{[1-(2-Fluoro-phenyl)-5-hydroxy-1H- 468.06 2.94 LC8 Cpyrazole-3-carbonyl]-amino}-3-(2-methoxy-5-trifluoromethyl-phenyl)-propionic acid 5553-(2-Fluoro-4-methyl-phenyl)-3-{[1-(2-fluoro- 402.1 2.84 LC8 Bphenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid 5563-{[1-(2-Fluoro-phenyl)-5-hydroxy-1H- 476.14 3.09 LC8 Cpyrazole-3-carbonyl]-amino}-3-(4-methoxy- biphenyl-3-yl)-propionic acid557 3-{[1-(2-Chloro-phenyl)-5-hydroxy-1H- 453.12 2.40 LC8 Bpyrazole-3-carbonyl]-amino}-3-(4- [1,2,4]triazol-1-yl-phenyl)-propionicacid 558 3-{[1-(2-Chloro-phenyl)-5-hydroxy-1H- 492.13 3.15 LC8 Bpyrazole-3-carbonyl]-amino}-3-(3-methoxy- biphenyl-4-yl)-propionic acid559 3-{[1-(2-Chloro-phenyl)-5-hydroxy-1H- 434.07 2.78 LC8 Bpyrazole-3-carbonyl]-amino}-3-(2-fluoro-5- methoxy-phenyl)-propionicacid 560 3-{[1-(2-Chloro-phenyl)-5-hydroxy-1H- 484.05 2.98 LC8 Cpyrazole-3-carbonyl]-amino}-3-(2-methoxy-5-trifluoromethyl-phenyl)-propionic acid 5613-{[1-(2-Chloro-phenyl)-5-hydroxy-1H- 418.08 2.88 LC8 Bpyrazole-3-carbonyl]-amino}-3-(2-fluoro-4- methyl-phenyl)-propionic acid562 3-{[1-(2-Chloro-phenyl)-5-hydroxy-1H- 492.13 3.12 LC8 Cpyrazole-3-carbonyl]-amino}-3-(4-methoxy- biphenyl-3-yl)-propionic acid563 3-[(5-Hydroxy-1-phenyl-1H-pyrazole-3- 419.11 2.46 LC8 Ccarbonyl)-amino]-3-(4-[1,2,4]triazol-1-yl- phenyl)-propionic acid 5643-(2-Fluoro-4-methyl-phenyl)-3-[(5-hydroxy- 384.13 2.91 LC8 B1-phenyl-1H-pyrazole-3-carbonyl)-amino]- propionic acid 5653-[(5-Hydroxy-1-phenyl-1H-pyrazole-3- 421.2 2.57 LC8 Ccarbonyl)-amino]-3-(4-pyrrolidin-1-yl- phenyl)-propionic acid 5663-{[1-(2-Fluoro-phenyl)-5-hydroxy-1H- 439.18 2.48 LC8 Cpyrazole-3-carbonyl]-amino}-3-(4-pyrrolidin- 1-yl-phenyl)-propionic acid567 3-{[1-(2-Chloro-phenyl)-5-hydroxy-1H- 484.09 2.93 LC8 Cpyrazole-3-carbonyl]-amino}-3-(4-methoxy-2-trifluoromethyl-phenyl)-propionic acid 5683-{[1-(2-Chloro-phenyl)-5-hydroxy-1H- 455.16 2.54 LC8 Cpyrazole-3-carbonyl]-amino}-3-(4-pyrrolidin- 1-yl-phenyl)-propionic acid569 3-(4′-Fluoro-biphenyl-4-yl)-3-{[5-hydroxy-1- 514.08 3.16 LC8 B(2-trifluoromethyl-phenyl)-1H-pyrazole-3- carbonyl]-amino}-propionicacid 570 (S)-3-{[1-(2-Fluoro-phenyl)-5-hydroxy-1H- 426.14 3.31 LC8pyrazole-3-carbonyl]-amino}-3-o-tolyl- propionic acid isopropyl ester571 (S)-3-{[1-(2-Fluoro-phenyl)-5-hydroxy-1H- 426.15 3.33 LC8pyrazole-3-carbonyl]-amino}-3-o-tolyl- propionic acid propyl ester 572(S)-3-[(1-Cyclopentyl-5-hydroxy-1H- 358.15 2.89 LC8 Bpyrazole-3-carbonyl)-amino]-3-o-tolyl- propionic acid 573(S)-3-[(1-Cyclohexyl-5-hydroxy-1H-pyrazole- 372.15 2.99 LC8 A3-carbonyl)-amino]-3-o-tolyl-propionic acid 5743-[(1-Cyclopentyl-5-hydroxy-1H-pyrazole-3- 438.14 3.17 LC8 Ccarbonyl)-amino]-3-(4′-fluoro-biphenyl-4-yl)- propionic acid 5753-[(1-Cyclohexyl-5-hydroxy-1H-pyrazole-3- 452.14 3.27 LC8 Ccarbonyl)-amino]-3-(4′-fluoro-biphenyl-4-yl)- propionic acid 5763-{[1-(2-Fluoro-phenyl)-5-hydroxy-1H- 514.09 3.28 LC8 Bpyrazole-3-carbonyl]-amino}-3-(4′-trifluoromethyl-biphenyl-4-yl)-propionic acid 577(S)-3-{[1-(2-Fluoro-phenyl)-5-hydroxy-1H- 440.13 3.47 LC8pyrazole-3-carbonyl]-amino}-3-o-tolyl- propionic acid butyl ester 5783-[(5-Hydroxy-1-phenyl-1H-pyrazole-3- 416.31 3.65 LC4 Ccarbonyl)-amino]-3-(4-pyrazol-1-yl-phenyl)- [(M − H)⁻] propionic acid579 3-[(5-Hydroxy-1-phenyl-1H-pyrazole-3- 496.1 3.35 LC8 Ccarbonyl)-amino]-3-(4′-trifluoromethyl- biphenyl-4-yl)-propionic acid580 3-{[1-(2-Chloro-phenyl)-5-hydroxy-1H- 452.08 2.69 LC8 Bpyrazole-3-carbonyl]-amino}-3-(4-pyrazol-1- yl-phenyl)-propionic acid581 3-{[1-(2-Chloro-phenyl)-5-hydroxy-1H- 530.06 3.32 LC8 Cpyrazole-3-carbonyl]-amino}-3-(4′-trifluoromethyl-biphenyl-4-yl)-propionic acid 5823-{[1-(2-Fluoro-phenyl)-5-hydroxy-1H- 436.1 2.66 LC8 Bpyrazole-3-carbonyl]-amino}-3-(4-pyrazol-1- yl-phenyl)-propionic acid583 3-(2′-Fluoro-biphenyl-4-yl)-3-[(5-hydroxy-1- 446.09 3.13 LC8 Cphenyl-1H-pyrazole-3-carbonyl)-amino]- propionic acid 5843-(2′-Fluoro-biphenyl-4-yl)-3-{[1-(2-fluoro- 464.09 3.06 LC8 Bphenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid 5853-{[1-(2-Chloro-phenyl)-5-hydroxy-1H- 480.09 3.09 LC8 Bpyrazole-3-carbonyl]-amino}-3-(2′-fluoro- biphenyl-4-yl)-propionic acid586 (S)-3-{[1-(3,5-Difluoro-phenyl)-5-hydroxy- 402.1 3.04 LC8 B1H-pyrazole-3-carbonyl]-amino}-3-o-tolyl- propionic acid 5873-{[1-(3,5-Difluoro-phenyl)-5-hydroxy-1H- 482.11 3.31 LC8 Cpyrazole-3-carbonyl]-amino}-3-(4′-fluoro- biphenyl-4-yl)-propionic acid588 (S)-3-{[1-(2,6-Difluoro-phenyl)-5-hydroxy- 402.08 2.78 LC8 B1H-pyrazole-3-carbonyl]-amino}-3-o-tolyl- propionic acid 589(S)-3-{[1-(3-Chloro-2-fluoro-phenyl)-5- 418.05 2.94 LC8 Bhydroxy-1H-pyrazole-3-carbonyl]-amino}-3- o-tolyl-propionic acid 5903-{[1-(3-Chloro-2-fluoro-phenyl)-5-hydroxy- 498.06 3.22 LC8 B1H-pyrazole-3-carbonyl]-amino}-3-(4′-fluoro- biphenyl-4-yl)-propionicacid 591 3-(2′-Chloro-biphenyl-4-yl)-3-{[1-(2-chloro- 496.07 3.18 LC8 Bphenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid 5923-{[1-(2-Fluoro-phenyl)-5-hydroxy-4-methyl- 398.15 2.83 LC8 B1H-pyrazole-3-carbonyl]-amino}-3-o-tolyl- propionic acid 593(S)-3-{[4-Chloro-1-(2-fluoro-phenyl)-5- 432.13 3.17 LC8 Bmethoxy-1H-pyrazole-3-carbonyl]-amino}-3- o-tolyl-propionic acid 594(S)-3-{[4-Bromo-1-(2-fluoro-phenyl)-5- 476.06 3.19 LC8 Amethoxy-1H-pyrazole-3-carbonyl]-amino}-3- o-tolyl-propionic acid 595(S)-3-{[4-Fluoro-1-(2-fluoro-phenyl)-5- 416.13 2.63 LC5 Amethoxy-1H-pyrazole-3-carbonyl]-amino}-3- o-tolyl-propionic acid 596(S)-3-(2,3-Dichloro-phenyl)-3-[(5-methoxy-1- 434.03 3.23 LC8 Aphenyl-1H-pyrazole-3-carbonyl)-amino]- propionic acid 5973-[(5-Methoxy-1-phenyl-1H-pyrazole-3- 443.16 2.46 LC8 Bcarbonyl)-amino]-3-(4-pyridin-2-yl-phenyl)- propionic acid 5983-{[1-(2-Fluoro-phenyl)-5-methoxy-1H- 461.13 2.42 LC8 Apyrazole-3-carbonyl]-amino}-3-(4-pyridin-2- yl-phenyl)-propionic acid599 (S)-3-{[1-(2,5-Difluoro-phenyl)-5-hydroxy- 402.12 2.06 LC7 A1H-pyrazole-3-carbonyl]-amino}-3-o-tolyl- propionic acid 6003-[(5-Hydroxy-1-phenyl-1H-pyrazole-3- 430.09 1.86 LC7 Ccarbonyl)-amino]-3-(4-methanesulfonyl- phenyl)-propionic acid 601(S)-3-{[5-Hydroxy-1-(3-sulfamoyl-phenyl)- 445.12 1.89 LC7 B1H-pyrazole-3-carbonyl]-amino}-3-o-tolyl- propionic acid 602(S)-3-{[5-Hydroxy-1-(4-sulfamoyl-phenyl)- 445.12 1.88 LC7 C1H-pyrazole-3-carbonyl]-amino}-3-o-tolyl- propionic acid 6033-{[1-(2-Fluoro-phenyl)-5-hydroxy-1H- 448.08 1.83 LC7 Cpyrazole-3-carbonyl]-amino}-3-(4- methanesulfonyl-phenyl)-propionic acid604 3-{[2-(2-Fluoro-phenyl)-5-methoxy-4-methyl- 412.15 3.16 LC82H-pyrazole-3-carbonyl]-amino}-3-o-tolyl- propionic acid 6053-{[1-(2-Fluoro-phenyl)-5-methoxy-4-methyl- 412.13 1.91 LC7 C1H-pyrazole-3-carbonyl]-amino}-3-o-tolyl- propionic acid 6063-(4′-Fluoro-biphenyl-4-yl)-3-{[5-hydroxy-1- 523.39 3.94 LC4 B(3-sulfamoyl-phenyl)-1H-pyrazole-3- [(M − H)⁻]carbonyl]-amino}-propionic acid 607(S)-3-{[5-Hydroxy-1-(2-methanesulfonyl- 444.14 1.93 LC7 Cphenyl)-1H-pyrazole-3-carbonyl]-amino}-3-o- tolyl-propionic acid 608(S)-3-{[1-(2-Chloro-phenyl)-5-methoxy-1H- 414.12 2.20 LC6 Bpyrazole-3-carbonyl]-amino}-3-o-tolyl- propionic acid 609(S)-3-{[1-(3-Fluoro-phenyl)-5-methoxy-1H- 398.15 2.26 LC6 Apyrazole-3-carbonyl]-amino}-3-o-tolyl- propionic acid 610(S)-3-{[1-(2,5-Difluoro-phenyl)-5-methoxy- 416.15 2.20 LC6 A1H-pyrazole-3-carbonyl]-amino}-3-o-tolyl- propionic acid 611(S)-3-[(1-tert-Butyl-5-methoxy-1H-pyrazole- 360.11 2.25 LC6 B3-carbonyl)-amino]-3-o-tolyl-propionic acid 612(S)-3-{[5-Cyclopropylmethoxy-1-(2-fluoro- 438.17 2.35 LC6 Aphenyl)-1H-pyrazole-3-carbonyl]-amino}-3-o- tolyl-propionic acid 613Pyrrolidine-1-carboxylic acid 5-((S)-2- 481.21 2.25 LC6 Acarboxy-1-o-tolyl-ethylcarbamoyl)-2-(2- fluoro-phenyl)-2H-pyrazol-3-ylester 614 (S)-3-{[5-Dimethylcarbamoyloxy-1-(2-fluoro- 455.17 2.15 LC6 Aphenyl)-1H-pyrazole-3-carbonyl]-amino}-3-o- tolyl-propionic acid 615(S)-3-{[5-Dimethylcarbamoylmethoxy-1-(2- 469.15 2.99 LC3 Afluoro-phenyl)-1H-pyrazole-3-carbonyl]- amino}-3-o-tolyl-propionic acid616 (S)-3-{[1-(2-Fluoro-phenyl)-5-(2-oxo-2- 495.17 3.07 LC3 Apyrrolidin-1-yl-ethoxy)-1H-pyrazole-3-carbonyl]-amino}-3-o-tolyl-propionic acid 617(S)-3-{[1-(2-Fluoro-phenyl)-5-(2-methoxy- 442.25 3.20 LC3 Aethoxy)-1H-pyrazole-3-carbonyl]-amino}-3-o- tolyl-propionic acid 618(S)-3-{[1-(2-Fluoro-phenyl)-5-methoxy-1H-pyrazole-3-carbonyl]-amino}-3-o-tolyl- propionic acid ethyl ester 619Piperidine-1-carboxylic acid 5-((S)-2- 495.22 1.70 LC9 Acarboxy-1-o-tolyl-ethylcarbamoyl)-2-(2- fluoro-phenyl)-2H-pyrazol-3-ylester 620 (S)-3-{[1-(2-Fluoro-phenyl)-5-(methyl- 517.2 1.71 LC9 Aphenyl-carbamoyloxy)-1H-pyrazole-3- carbonyl]-amino}-3-o-tolyl-propionicacid 621 (S)-3-[(5-Ethoxy-1-phenyl-1H-pyrazole-3- 394.18 1.69 LC9 Acarbonyl)-amino]-3-o-tolyl-propionic acid 622(S)-3-[(5-Cyclopropylmethoxy-1-phenyl-1H- 420.19 1.77 LC9 Apyrazole-3-carbonyl)-amino]-3-o-tolyl- propionic acid 623(S)-3-{[1-(2-Fluoro-phenyl)-5-(2- 542.22 1.28 LC11 Btrifluoromethyl-benzyloxy)-1H-pyrazole-3-carbonyl]-amino}-3-o-tolyl-propionic acid 624(S)-3-{[1-(2-Fluoro-phenyl)-5-(3- 542.31 3.89 LC3 Btrifluoromethyl-benzyloxy)-1H-pyrazole-3-carbonyl]-amino}-3-o-tolyl-propionic acid 625(S)-3-{[1-(2-Fluoro-phenyl)-5-phenethyloxy- 488.35 3.70 LC3 A1H-pyrazole-3-carbonyl]-amino}-3-o-tolyl- propionic acid 626(S)-3-{[5-Cyclopentyloxy-1-(2-fluoro-phenyl)- 452.32 3.68 LC3 A1H-pyrazole-3-carbonyl]-amino}-3-o-tolyl- propionic acid 627(S)-3-{[1-(2-Fluoro-phenyl)-5-(tetrahydro- 482.36 3.34 LC3 Apyran-4-ylmethoxy)-1H-pyrazole-3- carbonyl]-amino}-3-o-tolyl-propionicacid 628 (S)-3-{[5-[2-(3,5-Dimethyl-isoxazol-4-yl)- 507.27 1.18 LC11 Aethoxy]-1-(2-fluoro-phenyl)-1H-pyrazole-3-carbonyl]-amino}-3-o-tolyl-propionic acid 629(S)-3-{[1-(2-Fluoro-phenyl)-5-(pyridin-4- 475.33 2.62 LC3 Aylmethoxy)-1H-pyrazole-3-carbonyl]-amino}- 3-o-tolyl-propionic acid 630(S)-3-{[1-(2-Fluoro-phenyl)-5-isopropoxy-1H- 426.3 3.42 LC3 Apyrazole-3-carbonyl]-amino}-3-o-tolyl- propionic acid 631(S)-3-{[5-Cyclohexyloxy-1-(2-fluoro-phenyl)- 466.35 3.85 LC3 A1H-pyrazole-3-carbonyl]-amino}-3-o-tolyl- propionic acid 632(S)-3-{[5-(2,2-Dimethyl-propoxy)-1-(2-fluoro- 454.35 3.80 LC3 Aphenyl)-1H-pyrazole-3-carbonyl]-amino}-3-o- tolyl-propionic acid 633(S)-3-{[1-(2-Fluoro-phenyl)-5-isobutoxy-1H- 440.31 3.65 LC3 NOpyrazole-3-carbonyl]-amino}-3-o-tolyl- DATA propionic acid 634(S)-3-{[5-Cyclopropylmethoxy-1-(2,6- 456.31 3.54 LC3 Adifluoro-phenyl)-1H-pyrazole-3-carbonyl]- amino}-3-o-tolyl-propionicacid 635 (S)-3-{[5-(2-Cyano-benzyloxy)-1-(2-fluoro- 499.26 3.42 LC3 Aphenyl)-1H-pyrazole-3-carbonyl]-amino}-3-o- tolyl-propionic acid 636(S)-3-{[1-(2-Fluoro-phenyl)-5-(2-hydroxy-2- 518.34 1.27 LC11 Aphenyl-propoxy)-1H-pyrazole-3-carbonyl]- amino}-3-p-tolyl-propionic acid637 (S)-3-{[5-[2-(2-Ethoxy-ethoxy)-ethoxy]-1-(2- 500.3 3.32 LC3 Afluoro-phenyl)-1H-pyrazole-3-carbonyl]- amino}-3-o-tolyl-propionic acid638 (S)-3-{[5-Cyclohexylmethoxy-1-(2-fluoro- 480.3 1.33 LC11 Aphenyl)-1H-pyrazole-3-carbonyl]-amino}-3-o- tolyl-propionic acid 639(S)-3-({1-(2-Fluoro-phenyl)-5-[2-(2-oxo- 495.3 2.93 LC3 Apyrrolidin-1-yl)-ethoxy]-1H-pyrazole-3-carbonyl}-amino)-3-o-tolyl-propionic acid 640(S)-3-{[1-(2-Fluoro-phenyl)-5-(pyridin-2- 475.31 2.93 LC3 Aylmethoxy)-1H-pyrazole-3-carbonyl]-amino}- 3-o-tolyl-propionic acid 641(S)-3-{[1-(2-Fluoro-phenyl)-5-(3-fluoro- 444.26 3.39 LC3 Apropoxy)-1H-pyrazole-3-carbonyl]-amino}-3- o-tolyl-propionic acid 642(S)-3-{[1-(2-Fluoro-phenyl)-5-(tetrahydro- 468.27 3.24 LC3 Afuran-2-ylmethoxy)-1H-pyrazole-3-carbonyl]- amino}-3-o-tolyl-propionicacid 643 (S)-3-{[1-(2-Fluoro-phenyl)-5-(3-methyl- 479.24 3.30 LC3 Aisoxazol-5-ylmethoxy)-1H-pyrazole-3-carbonyl]-amino}-3-o-tolyl-propionic acid 644(S)-3-{[5-(2,6-Difluoro-benzyloxy)-1-(2- 510.26 3.60 LC3 Afluoro-phenyl)-1H-pyrazole-3-carbonyl]- amino}-3-o-tolyl-propionic acid645 (S)-3-{[5-(2,2-Difluoro-cyclopropylmethoxy)- 474.12 1.70 LC9 A1-(2-fluoro-phenyl)-1H-pyrazole-3-carbonyl]- amino}-3-o-tolyl-propionicacid 646 (S)-3-{[1-(2-Fluoro-phenyl)-5-(2-methyl- 495.1 1.60 LC9 Athiazol-4-ylmethoxy)-1H-pyrazole-3- carbonyl]-amino}-3-o-tolyl-propionicacid 647 (S)-3-{[1-(2-Fluoro-phenyl)-5-(isoxazol-3- 465.27 3.20 LC3 Aylmethoxy)-1H-pyrazole-3-carbonyl]-amino}- 3-o-tolyl-propionic acid 648(S)-3-{[5-Cyclobutoxy-1-(2-fluoro-phenyl)- 438.28 3.50 LC3 A1H-pyrazole-3-carbonyl]-amino}-3-o-tolyl- propionic acid 649(S)-3-{[5-Cyclobutylmethoxy-1-(2-fluoro- 452.29 3.68 LC3 Aphenyl)-1H-pyrazole-3-carbonyl]-amino}-3-o- tolyl-propionic acid 650(S)-3-{[1-(2-Fluoro-phenyl)-5-(tetrahydro- 468.3 3.18 LC3 Afuran-3-ylmethoxy)-1H-pyrazole-3-carbonyl]- amino}-3-o-tolyl-propionicacid 651 (S)-3-{[5-Benzyloxy-1-(2-fluoro-phenyl)-1H- 474.28 3.65 LC3 Apyrazole-3-carbonyl]-amino}-3-o-tolyl- propionic acid 652(S)-3-{[1-(2-Fluoro-phenyl)-5-((R)-5-oxo- 481.29 1.40 LC9 Apyrrolidin-2-ylmethoxy)-1H-pyrazole-3-carbonyl]-amino}-3-o-tolyl-propionic acid 653(S)-3-{[1-(2-Fluoro-phenyl)-5-(tetrahydro- 482.31 3.47 LC3 Apyran-2-ylmethoxy)-1H-pyrazole-3- carbonyl]-amino}-3-o-tolyl-propionicacid 654 (S)-3-{[1-(2-Fluoro-phenyl)-5-((S)-5-oxo- 481.21 1.42 LC9 Apyrrolidin-2-ylmethoxy)-1H-pyrazole-3-carbonyl]-amino}-3-o-tolyl-propionic acid 655(S)-3-{[1-(2-Fluoro-phenyl)-5-(3-methoxy- 504.3 3.65 LC3 Abenzyloxy)-1H-pyrazole-3-carbonyl]-amino}- 3-o-tolyl-propionic acid 656(S)-3-{[1-(2-Fluoro-phenyl)-5-(1-methyl-1H- 478.26 1.53 LC9pyrazol-3-ylmethoxy)-1H-pyrazole-3- carbonyl]-amino}-3-o-tolyl-propionicacid 657 (S)-3-{[1-(2-Fluoro-phenyl)-5-(5-methyl- 479.25 1.18 LC11 Aisoxazol-3-ylmethoxy)-1H-pyrazole-3-carbonyl]-amino}-3-o-tolyl-propionic acid 658(S)-3-{[1-(2-Fluoro-phenyl)-5-(isoxazol-5- 465.25 1.11 LC11 Aylmethoxy)-1H-pyrazole-3-carbonyl]-amino}- 3-o-tolyl-propionic acid 659(S)-3-{[5-(3,3-Dimethyl-butoxy)-1-(2-fluoro- 468.24 1.90 LC9 Aphenyl)-1H-pyrazole-3-carbonyl]-amino}-3-o- tolyl-propionic acid 660(S)-3-{[1-(2-Fluoro-phenyl)-5-hexyloxy-1H- 468.29 1.33 LC11 Apyrazole-3-carbonyl]-amino}-3-o-tolyl- propionic acid 6611-(2-Fluoro-phenyl)-5-methoxy-1H-pyrazole- 397.19 3.67 LC12 3-carboxylicacid ((S)-2-carbamoyl-1-o-tolyl- ethyl)-amide 662(S)-3-{[5-Ethoxy-1-(2-fluoro-phenyl)-1H- 412.19 1.60 LC9 Apyrazole-3-carbonyl]-amino}-3-o-tolyl- propionic acid 663(S)-3-{[1-(2-Fluoro-phenyl)-5-(3-methyl- 468.23 1.57 LC9 Aoxetan-3-ylmethoxy)-1H-pyrazole-3- carbonyl]-amino}-3-o-tolyl-propionicacid 664 3-(3-Fluoro-2-methyl-phenyl)-3-{[1-(2-fluoro- 416.14 1.57 LC9 Aphenyl)-5-methoxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid 665(S)-3-{[1-(2-Fluoro-phenyl)-5-methoxy-1H- 384.14 1.49 LC9 Apyrazole-3-carbonyl]-amino}-3-phenyl- propionic acid 6663-(2,4-Dimethyl-phenyl)-3-{[1-(2-fluoro- 412.17 1.61 LC9 Aphenyl)-5-methoxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid 667(S)-3-{[1-(2-Fluoro-phenyl)-5-methoxy-1H- 414.16 1.54 LC9 Bpyrazole-3-carbonyl]-amino}-3-(2-methoxy- phenyl)-propionic acid 668(S)-3-(4-Cyano-phenyl)-3-{[1-(2-fluoro- 409.14 1.47 LC9 Bphenyl)-5-methoxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid 669(S)-3-{[1-(2-Fluoro-phenyl)-5-methoxy-1H- 414.16 1.51 LC9 Bpyrazole-3-carbonyl]-amino}-3-(3-methoxy- phenyl)-propionic acid 670(S)-3-{[1-(2-Fluoro-phenyl)-5-methoxy-1H- 398.16 1.56 LC9 Apyrazole-3-carbonyl]-amino}-3-m-tolyl- propionic acid 671(S)-3-(4-Chloro-phenyl)-3-{[1-(2-fluoro- 418.11 1.59 LC9 Aphenyl)-5-methoxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid 6723-{[1-(2-Fluoro-phenyl)-5-methoxy-1H- 428.18 1.54 LC9 Apyrazole-3-carbonyl]-amino}-3-(4-methoxy- 2-methyl-phenyl)-propionicacid 673 (S)-3-(2,4-Dichloro-phenyl)-3-{[1-(2-fluoro- 452.07 1.65 LC9 Aphenyl)-5-methoxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid 674(S)-3-{[1-(2-Fluoro-phenyl)-5-methoxy-1H- 452.12 1.63 LC9 Apyrazole-3-carbonyl]-amino}-3-(4- trifluoromethyl-phenyl)-propionic acid675 (S)-3-{[1-(2-Fluoro-phenyl)-5-methoxy-1H- 398.16 1.55 LC9 Apyrazole-3-carbonyl]-amino}-3-p-tolyl- propionic acid 676(S)-3-(2-Chloro-phenyl)-3-{[1-(2-fluoro- 418.11 1.55 LC9 Aphenyl)-5-methoxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid 6773-(4-Fluoro-2-methyl-phenyl)-3-{[1-(2-fluoro- 416.16 1.57 LC9 Aphenyl)-5-methoxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid 6783-(4-Fluoro-phenyl)-3-{[1-(2-fluoro-phenyl)- 402.14 1.52 LC9 B5-methoxy-1H-pyrazole-3-carbonyl]-amino}- propionic acid 679(S)-3-(2-Fluoro-phenyl)-3-{[1-(2-fluoro- 402.14 1.50 LC9 Bphenyl)-5-methoxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid 680(S)-3-{[1-(2-Fluoro-phenyl)-5-methoxy-1H- 452.21 1.18 LC11 Bpyrazole-3-carbonyl]-amino}-3-(2- trifluoromethyl-phenyl)-propionic acid681 (S)-3-(2,3-Dichloro-phenyl)-3-{[1-(2-fluoro- 452.07 1.63 LC9 Aphenyl)-5-methoxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid 6823-(2,3-Dimethyl-phenyl)-3-{[1-(2-fluoro- 412.19 1.60 LC9 Aphenyl)-5-methoxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid 6833-(2,5-Dichloro-phenyl)-3-{[1-(2-fluoro- 452.07 1.64 LC9 Aphenyl)-5-methoxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid 6843-{[5-Cyclopropylmethoxy-1-(2-fluoro- 456.17 1.70 LC9 Aphenyl)-1H-pyrazole-3-carbonyl]-amino}-3-(3-fluoro-2-methyl-phenyl)-propionic acid 685(S)-3-{[5-Cyclopropylmethoxy-1-(2-fluoro- 424.18 1.63 LC9 Aphenyl)-1H-pyrazole-3-carbonyl]-amino}-3- phenyl-propionic acid 6863-{[5-Cyclopropylmethoxy-1-(2-fluoro- 452.22 1.73 LC9 Aphenyl)-1H-pyrazole-3-carbonyl]-amino}-3-(2,4-dimethyl-phenyl)-propionic acid 687(S)-3-{[5-Cyclopropylmethoxy-1-(2-fluoro- 454.2 1.66 LC9 Bphenyl)-1H-pyrazole-3-carbonyl]-amino}-3- (2-methoxy-phenyl)-propionicacid 688 (S)-3-(4-Cyano-phenyl)-3-{[5- 449.18 1.61 LC9 Acyclopropylmethoxy-1-(2-fluoro-phenyl)-1H-pyrazole-3-carbonyl]-amino}-propionic acid 689(S)-3-{[5-Cyclopropylmethoxy-1-(2-fluoro- 454.19 1.63 LC9 Bphenyl)-1H-pyrazole-3-carbonyl]-amino}-3- (3-methoxy-phenyl)-propionicacid 690 (S)-3-{[5-Cyclopropylmethoxy-1-(2-fluoro- 438.2 1.69 LC9 Aphenyl)-1H-pyrazole-3-carbonyl]-amino}-3- m-tolyl-propionic acid 691(S)-3-(4-Chloro-phenyl)-3-{[5- 458.15 1.71 LC9 Bcyclopropylmethoxy-1-(2-fluoro-phenyl)-1H-pyrazole-3-carbonyl]-amino}-propionic acid 6923-{[5-Cyclopropylmethoxy-1-(2-fluoro- 468.22 1.67 LC9 Aphenyl)-1H-pyrazole-3-carbonyl]-amino}-3-(4-methoxy-2-methyl-phenyl)-propionic acid 693(S)-3-{[5-Cyclopropylmethoxy-1-(2-fluoro- 492.11 1.77 LC9 Bphenyl)-1H-pyrazole-3-carbonyl]-amino}-3-(2,4-dichloro-phenyl)-propionic acid 694(S)-3-{[5-Cyclopropylmethoxy-1-(2-fluoro- 492.16 1.75 LC9 Aphenyl)-1H-pyrazole-3-carbonyl]-amino}-3-(4-trifluoromethyl-phenyl)-propionic acid 695(S)-3-{[5-Cyclopropylmethoxy-1-(2-fluoro- 438.21 1.69 LC9 Aphenyl)-1H-pyrazole-3-carbonyl]-amino}-3-p- tolyl-propionic acid 696(S)-3-(2-Chloro-phenyl)-3-{[5- 458.15 1.68 LC9 Acyclopropylmethoxy-1-(2-fluoro-phenyl)-1H-pyrazole-3-carbonyl]-amino}-propionic acid 6973-{[5-Cyclopropylmethoxy-1-(2-fluoro- 456.2 1.70 LC9phenyl)-1H-pyrazole-3-carbonyl]-amino}-3-(4-fluoro-2-methyl-phenyl)-propionic acid 6983-{[5-Cyclopropylmethoxy-1-(2-fluoro- 442.24 1.21 LC11 Bphenyl)-1H-pyrazole-3-carbonyl]-amino}-3- (4-fluoro-phenyl)-propionicacid 699 (S)-3-{[5-Cyclopropylmethoxy-1-(2-fluoro- 442.23 1.21 LC11 Bphenyl)-1H-pyrazole-3-carbonyl]-amino}-3- (2-fluoro-phenyl)-propionicacid 700 (S)-3-{[5-(3,3-Dimethyl-2-oxo-butoxy)-1-(2- 482.18 1.67 LC9 Afluoro-phenyl)-1H-pyrazole-3-carbonyl]- amino}-3-o-tolyl-propionic acid701 (S)-3-{[5-Cyclopropylmethoxy-1-(2-fluoro- 492.16 1.72 LC9 Bphenyl)-1H-pyrazole-3-carbonyl]-amino}-3-(2-trifluoromethyl-phenyl)-propionic acid 702(S)-3-{[5-Cyclopropylmethoxy-1-(2-fluoro- 492.11 1.74 LC9 Aphenyl)-1H-pyrazole-3-carbonyl]-amino}-3-(2,3-dichloro-phenyl)-propionic acid 7033-{[5-Cyclopropylmethoxy-1-(2-fluoro- 452.22 1.72 LC9 Aphenyl)-1H-pyrazole-3-carbonyl]-amino}-3-(2,3-dimethyl-phenyl)-propionic acid 7043-{[5-Cyclopropylmethoxy-1-(2-fluoro- 492.12 1.76 LC9 Aphenyl)-1H-pyrazole-3-carbonyl]-amino}-3-(2,5-dichloro-phenyl)-propionic acid 7053-(2-Chloro-4-methoxy-phenyl)-3-{[5- 488.18 1.70 LC9 Acyclopropylmethoxy-1-(2-fluoro-phenyl)-1H-pyrazole-3-carbonyl]-amino}-propionic acid 7063-{[5-Ethoxy-1-(2-fluoro-phenyl)-1H- 430.18 1.64 LC9 Apyrazole-3-carbonyl]-amino}-3-(3-fluoro-2- methyl-phenyl)-propionic acid707 (S)-3-{[5-Ethoxy-1-(2-fluoro-phenyl)-1H- 398.18 1.57 LC9 Bpyrazole-3-carbonyl]-amino}-3-phenyl- propionic acid 7083-(2,4-Dimethyl-phenyl)-3-{[5-ethoxy-1-(2- 426.21 1.67 LC9 Afluoro-phenyl)-1H-pyrazole-3-carbonyl]- amino}-propionic acid 709(S)-3-{[5-Ethoxy-1-(2-fluoro-phenyl)-1H- 428.19 1.60 LC9 Bpyrazole-3-carbonyl]-amino}-3-(2-methoxy- phenyl)-propionic acid 710(S)-3-(4-Cyano-phenyl)-3-{[5-ethoxy-1-(2- 423.21 1.14 LC11 Bfluoro-phenyl)-1H-pyrazole-3-carbonyl]- amino}-propionic acid 711(S)-3-{[5-Ethoxy-1-(2-fluoro-phenyl)-1H- 428.19 1.57 LC9 Bpyrazole-3-carbonyl]-amino}-3-(3-methoxy- phenyl)-propionic acid 712(S)-3-{[5-Ethoxy-1-(2-fluoro-phenyl)-1H- 412.22 1.20 LC11 Apyrazole-3-carbonyl]-amino}-3-m-tolyl- propionic acid 713(S)-3-(4-Chloro-phenyl)-3-{[5-ethoxy-1-(2- 432.14 1.21 LC11 Afluoro-phenyl)-1H-pyrazole-3-carbonyl]- amino}-propionic acid 7143-{[5-Ethoxy-1-(2-fluoro-phenyl)-1H- 442.23 1.19 LC11 Apyrazole-3-carbonyl]-amino}-3-(4-methoxy- 2-methyl-phenyl)-propionicacid 715 (S)-3-{[5-Ethoxy-1-(2-fluoro-phenyl)-1H- 466.18 1.23 LC11 Apyrazole-3-carbonyl]-amino}-3-(4- trifluoromethyl-phenyl)-propionic acid716 (S)-3-{[5-Ethoxy-1-(2-fluoro-phenyl)-1H- 412.16 1.60 LC9 Apyrazole-3-carbonyl]-amino}-3-p-tolyl- propionic acid 717(S)-3-(2-Chloro-phenyl)-3-{[5-ethoxy-1-(2- 432.14 1.20 LC11 Afluoro-phenyl)-1H-pyrazole-3-carbonyl]- amino}-propionic acid 7183-{[5-Ethoxy-1-(2-fluoro-phenyl)-1H- 430.21 1.20 LC11 Apyrazole-3-carbonyl]-amino}-3-(4-fluoro-2- methyl-phenyl)-propionic acid719 3-{[5-Ethoxy-1-(2-fluoro-phenyl)-1H- 416.19 1.18 LC11 Bpyrazole-3-carbonyl]-amino}-3-(4-fluoro- phenyl)-propionic acid 720(S)-3-{[5-Ethoxy-1-(2-fluoro-phenyl)-1H- 416.18 1.17 LC11 Apyrazole-3-carbonyl]-amino}-3-(2-fluoro- phenyl)-propionic acid 721(S)-3-{[5-Ethoxy-1-(2-fluoro-phenyl)-1H- 466.21 1.21 LC11 Bpyrazole-3-carbonyl]-amino}-3-(2- trifluoromethyl-phenyl)-propionic acid722 (S)-3-(2,3-Dichloro-phenyl)-3-{[5-ethoxy-1- 466.17 1.23 LC11 A(2-fluoro-phenyl)-1H-pyrazole-3-carbonyl]- amino}-propionic acid 7233-(2,3-Dimethyl-phenyl)-3-{[5-ethoxy-1-(2- 426.23 1.22 LC11 Afluoro-phenyl)-1H-pyrazole-3-carbonyl]- amino}-propionic acid 7243-(2-Chloro-4-methoxy-phenyl)-3-{[5-ethoxy- 461.64 1.20 LC11 A1-(2-fluoro-phenyl)-1H-pyrazole-3-carbonyl]- amino}-propionic acid 7253-{[1-(2-Chloro-phenyl)-5-ethoxy-1H- 446.15 1.22 LC11 Apyrazole-3-carbonyl]-amino}-3-(3-fluoro-2- methyl-phenyl)-propionic acid726 (S)-3-{[1-(2-Chloro-phenyl)-5-ethoxy-1H- 413.65 1.19 LC11 Bpyrazole-3-carbonyl]-amino}-3-phenyl- propionic acid 727(S)-3-{[1-(2-Chloro-phenyl)-5-ethoxy-1H- 428.13 1.21 LC11 Apyrazole-3-carbonyl]-amino}-3-o-tolyl- propionic acid 7283-{[1-(2-Chloro-phenyl)-5-ethoxy-1H- 442.2 1.24 LC11 Apyrazole-3-carbonyl]-amino}-3-(2,4-dimethyl- phenyl)-propionic acid 729(S)-3-{[1-(2-Chloro-phenyl)-5-ethoxy-1H- 443.66 1.20 LC11 Bpyrazole-3-carbonyl]-amino}-3-(2-methoxy- phenyl)-propionic acid 730(S)-3-{[1-(2-Chloro-phenyl)-5-ethoxy-1H- 439.17 1.16 LC11 Bpyrazole-3-carbonyl]-amino}-3-(4-cyano- phenyl)-propionic acid 731(S)-3-{[1-(2-Chloro-phenyl)-5-ethoxy-1H- 444.15 1.18 LC11 Bpyrazole-3-carbonyl]-amino}-3-(3-methoxy- phenyl)-propionic acid 732(S)-3-{[1-(2-Chloro-phenyl)-5-ethoxy-1H- 428.25 4.48 LC10 Apyrazole-3-carbonyl]-amino}-3-m-tolyl- propionic acid 733(S)-3-(4-Chloro-phenyl)-3-{[1-(2-chloro- 448.13 4.55 LC10 Aphenyl)-5-ethoxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid 7343-{[1-(2-Chloro-phenyl)-5-ethoxy-1H- 458.14 1.61 LC9pyrazole-3-carbonyl]-amino}-3-(4-methoxy- 2-methyl-phenyl)-propionicacid 735 (S)-3-{[1-(2-Chloro-phenyl)-5-ethoxy-1H- 482.08 1.72 LC9 Bpyrazole-3-carbonyl]-amino}-3-(4- trifluoromethyl-phenyl)-propionic acid736 (S)-3-{[1-(2-Chloro-phenyl)-5-ethoxy-1H- 428.13 1.63 LC9 Apyrazole-3-carbonyl]-amino}-3-p-tolyl- propionic acid 737(S)-3-(2-Chloro-phenyl)-3-{[1-(2-chloro- 448.1 1.64 LC9 Aphenyl)-5-ethoxy-1H-pyrazole-3-carbonyl]- amino}-propionic acid 7383-{[1-(2-Chloro-phenyl)-5-ethoxy-1H- 446.12 1.66 LC9 Apyrazole-3-carbonyl]-amino}-3-(4-fluoro-2- methyl-phenyl)-propionic acid739 3-{[1-(2-Chloro-phenyl)-5-ethoxy-1H- 432.11 1.61 LC9 Bpyrazole-3-carbonyl]-amino}-3-(4-fluoro- phenyl)-propionic acid 740(S)-3-{[1-(2-Chloro-phenyl)-5-ethoxy-1H- 432.1 1.60 LC9pyrazole-3-carbonyl]-amino}-3-(2-fluoro- phenyl)-propionic acid 741(S)-3-{[1-(2-Chloro-phenyl)-5-ethoxy-1H- 482.08 1.67 LC9 Bpyrazole-3-carbonyl]-amino}-3-(2- trifluoromethyl-phenyl)-propionic acid742 (S)-3-{[1-(2-Chloro-phenyl)-5-ethoxy-1H- 482.04 1.71 LC9 Apyrazole-3-carbonyl]-amino}-3-(2,3-dichloro- phenyl)-propionic acid 7433-{[1-(2-Chloro-phenyl)-5-ethoxy-1H- 442.16 1.68 LC9 Apyrazole-3-carbonyl]-amino}-3-(2,3-dimethyl- phenyl)-propionic acid 744(S)-3-{[1-(2-Fluoro-phenyl)-5-(2-hydroxy-3,3- 484.35 1.23 LC11 Adimethyl-butoxy)-1H-pyrazole-3-carbonyl]- amino}-3-o-tolyl-propionicacid 745 (S)-3-{[1-(2-Fluoro-phenyl)-5-((R)-2-hydroxy- 484.34 10.16 LC13A 3,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-3-o-tolyl-propionic acid (3) 746(S)-3-{[1-(2-Fluoro-phenyl)-5-((S)-2-hydroxy- 484.34 10.35 LC13 A3,3-dimethyl-butoxy)-1H-pyrazole-3- carbonyl]-amino}-3-o-tolyl-propionicacid (3) 747 (S)-3-{[1-(2-Fluoro-phenyl)-5-((R)-2-hydroxy- 498.3 10.53LC13 A 2,3,3-trimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-3-o-tolyl-propionic acid (3) 748(S)-3-{[1-(2-Fluoro-phenyl)-5-((S)-2-hydroxy- 498.3 10.80 LC13 A2,3,3-trimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-3-o-tolyl-propionic acid (3) 749(S)-3-{[1-(2-Fluoro-phenyl)-5-(2-hydroxy- 442.32 1.16 LC11 Apropoxy)-1H-pyrazole-3-carbonyl]-amino}-3- o-tolyl-propionic acid 750(S)-3-{[1-(2-Fluoro-phenyl)-5-(2-hydroxy-2- 470.35 4.19 LC10 Amethyl-butoxy)-1H-pyrazole-3-carbonyl]- amino}-3-o-tolyl-propionic acid751 (S)-3-(2,4-Dichloro-phenyl)-3-{[1-(2-fluoro- 510.25 4.34 LC10 Aphenyl)-5-(2-hydroxy-2-methyl-propoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic acid 752(S)-3-{[1-(2-Fluoro-phenyl)-5-(2-hydroxy-2- 456.38 3.97 LC10 Amethyl-propoxy)-1H-pyrazole-3-carbonyl]- amino}-3-o-tolyl-propionic acid753 (S)-3-(2,4-Dichloro-phenyl)-3-{[1-(2-fluoro- 538.24 1.31 LC11 Aphenyl)-5-((R)-2-hydroxy-3,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}- propionic acid (3) 754(S)-3-(2,4-Dichloro-phenyl)-3-{[1-(2-fluoro- 538.24 1.32 LC11 Aphenyl)-5-((S)-2-hydroxy-3,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}- propionic acid (3) 755(S)-3-{[1-(2-Fluoro-phenyl)-5-(2-hydroxy- 456.27 1.19 LC11 Abutoxy)-1H-pyrazole-3-carbonyl]-amino}-3-o- tolyl-propionic acid 756(S)-3-{[5-(2-Ethyl-2-hydroxy-butoxy)-1-(2- 484.32 1.26 LC11 Afluoro-phenyl)-1H-pyrazole-3-carbonyl]- amino}-3-o-tolyl-propionic acid757 (S)-3-{[5-(2-Cyclopropyl-2-hydroxy-propoxy)- 482.31 1.24 LC11 A1-(2-fluoro-phenyl)-1H-pyrazole-3-carbonyl]- amino}-3-o-tolyl-propionicacid 758 (S)-3-(2-Chloro-phenyl)-3-{[1-(2-fluoro- 518.28 1.29 LC11 Aphenyl)-5-((R)-2-hydroxy-2,3,3-trimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}- propionic acid (3) 759(S)-3-(2-Chloro-phenyl)-3-{[1-(2-fluoro- 518.3 1.30 LC11 Aphenyl)-5-((S)-2-hydroxy-2,3,3-trimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}- propionic acid (3) 760(S)-3-{[5-((R)-2-Cyclopropyl-2-hydroxy- 468.31 1.20 LC11 Aethoxy)-1-(2-fluoro-phenyl)-1H-pyrazole-3-carbonyl]-amino}-3-o-tolyl-propionic acid (3) 761(S)-3-{[5-((S)-2-Cyclopropyl-2-hydroxy- 468.31 1.21 LC11 Aethoxy)-1-(2-fluoro-phenyl)-1H-pyrazole-3-carbonyl]-amino}-3-o-tolyl-propionic acid (3) 762(S)-3-(2,4-Dichloro-phenyl)-3-{[5-(2-ethyl-2- 538.17 1.31 LC11 Ahydroxy-butoxy)-1-(2-fluoro-phenyl)-1H-pyrazole-3-carbonyl]-amino}-propionic acid 763(S)-3-{[5-((R)-2-Cyclopropyl-2-hydroxy- 482.23 1.24 LC11 Apropoxy)-1-(2-fluoro-phenyl)-1H-pyrazole-3-carbonyl]-amino}-3-o-tolyl-propionic acid (3) 764(S)-3-{[5-((S)-2-Cyclopropyl-2-hydroxy- 482.21 1.24 LC11 Apropoxy)-1-(2-fluoro-phenyl)-1H-pyrazole-3-carbonyl]-amino}-3-o-tolyl-propionic acid (3) 765(S)-3-{[1-(2-Fluoro-phenyl)-5-((R)-2- 484.36 10.01 LC14 Ahydroxy-2,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-3-o-tolyl-propionic acid 766(S)-3-{[1-(2-Fluoro-phenyl)-5-((S)-2- 484.28 1.26 LC11 Ahydroxy-2,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-3-p-tolyl-propionic acid 767(S)-3-(3-Chloro-phenyl)-3-{[1-(2-fluoro- 504.3 1.14 LC11 Aphenyl)-5-((R)-2-hydroxy-2,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}- propionic acid 768(S)-3-(4-Fluoro-phenyl)-3-{[1-(2-fluoro- 488.35 1.11 LC11 Aphenyl)-5-((R)-2-hydroxy-2,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}- propionic acid 769(S)-3-(2,3-Dimethoxy-phenyl)-3-{[1-(2- 530.34 1.25 LC11 Afluoro-phenyl)-5-((S)-2-hydroxy-2,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]- amino}-propionic acid 770(S)-3-{[1-(2-Fluoro-phenyl)-5-(2-hydroxy- 484.24 1.26 LC11 A2,3-dimethyl-butoxy)-1H-pyrazole-3- carbonyl]-amino}-3-o-tolyl-propionicacid 771 (S)-3-(4-Fluoro-phenyl)-3-{[1-(2-fluoro- 502.34 1.27 LC11 Aphenyl)-5-((R)-2-hydroxy-2,3,3-trimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}- propionic acid 772(S)-3-(2,4-Dimethyl-phenyl)-3-{[1-(2-fluoro- 498.31 1.29 LC11 Aphenyl)-5-((S)-2-hydroxy-2,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}- propionic acid 7733-Cyclohexyl-3-{[1-(2-fluoro-phenyl)-5-((S)- 490.29 4.68 LC10 A2-hydroxy-2,3,3-trimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic acid 774(S)-3-(3-Chloro-phenyl)-3-{[1-(2-fluoro- 518.23 1.17 LC11 Aphenyl)-5-((R)-2-hydroxy-2,3,3-trimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}- propionic acid 775(S)-3-(2-Chloro-phenyl)-3-{[1-(2-fluoro- 504.2 1.26 LC11 Aphenyl)-5-(2-hydroxy-2,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic acid 776(S)-3-(2,3-Dichloro-phenyl)-3-{[1-(2-fluoro- 538.15 1.3 LC11 Aphenyl)-5-((R)-2-hydroxy-3,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}- propionic acid 777(S)-3-(2-Chloro-phenyl)-3-{[5-(3,3-dimethyl- 502.15 1.28 LC11 A2-oxo-butoxy)-1-(2-fluoro-phenyl)-1H-pyrazole-3-carbonyl]-amino}-propionic acid 778(S)-3-(3-Cyano-phenyl)-3-{[1-(2-fluoro- 509.31 1.25 LC11 Aphenyl)-5-((R)-2-hydroxy-2,3,3-trimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}- propionic acid 779(S)-3-(3-Fluoro-phenyl)-3-{[1-(2-fluoro- 502.3 1.28 LC11 Aphenyl)-5-((R)-2-hydroxy-2,3,3-trimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}- propionic acid 780(S)-3-{[1-(2-Fluoro-phenyl)-5-((R)-2- 498.35 1.29 LC11 Ahydroxy-2,3,3-trimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-3-p-tolyl- propionic acid 781(S)-3-{[1-(2-Fluoro-phenyl)-5-((S)-2- 498.32 1.16 LC11 Ahydroxy-2,3,3-trimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-3-p-tolyl- propionic acid 782(S)-3-(3-Fluoro-phenyl)-3-{[1-(2-fluoro- 488.23 1.25 LC11 Aphenyl)-5-(2-hydroxy-2,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic acid 783(S)-3-{[1-(2-Fluoro-phenyl)-5-((S)-2- 500.33 1.25 LC11 Ahydroxy-2,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-3-(2-methoxy-phenyl)- propionic acid 784(S)-3-{[1-(2-Fluoro-phenyl)-5-((S)-2- 538.3 1.27 LC11 Ahydroxy-2,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-3-(2-trifluoromethyl- phenyl)-propionic acid 785(S)-3-(3-Chloro-phenyl)-3-{[1-(2-fluoro- 504.2 1.28 LC11 Aphenyl)-5-(2-hydroxy-2,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic acid 7863-Cyclohexyl-3-{[1-(2-fluoro-phenyl)-5-((R)- 476.4 1.16 LC11 A2-hydroxy-2,3-dimethyl-butoxy)-1H- pyrazole-3-carbonyl]-amino}-propionicacid 787 (S)-3-{[1-(2-Fluoro-phenyl)-5-(2-hydroxy- 484.25 1.27 LC11 A2,3-dimethyl-butoxy)-1H-pyrazole-3- carbonyl]-amino}-3-p-tolyl-propionicacid 788 (S)-3-{[1-(2-Fluoro-phenyl)-5-((R)-2- 484.29 1.14 LC11 Ahydroxy-3,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-3-p-tolyl-propionic acid 789(S)-3-(2-Chloro-phenyl)-3-{[1-(2-fluoro- 518.3 1.3 LC11 Aphenyl)-5-((S)-2-hydroxy-2,3,3-trimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}- propionic acid 790(S)-3-(2-Chloro-phenyl)-3-{[1-(2-fluoro- 518.28 1.29 LC11 Aphenyl)-5-((R)-2-hydroxy-2,3,3-trimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}- propionic acid 791(S)-3-{[5-(3,3-Dimethyl-2-oxo-butoxy)-1-(2- 482.2 1.28 LC11 Afluoro-phenyl)-1H-pyrazole-3-carbonyl]- amino}-3-p-tolyl-propionic acid792 (S)-3-{[1-(2-Fluoro-phenyl)-5-((S)-2- 484.36 10.46 LC14 Ahydroxy-3,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-3-m-tolyl-propionic acid 793(S)-3-(2-Chloro-phenyl)-3-{[1-(2-fluoro- 504.17 1.27 LC11 Aphenyl)-5-((R)-2-hydroxy-3,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}- propionic acid 794(S)-3-(4-Chloro-phenyl)-3-{[1-(2-fluoro- 504.18 1.28 LC11 Aphenyl)-5-((S)-2-hydroxy-3,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}- propionic acid 795(S)-3-(3-Chloro-phenyl)-3-{[1-(2-fluoro- 504.31 10.5 LC11 Aphenyl)-5-((R)-2-hydroxy-3,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}- propionic acid 796(S)-3-(3-Chloro-phenyl)-3-{[5-(3,3-dimethyl- 502.17 1.29 LC11 A2-oxo-butoxy)-1-(2-fluoro-phenyl)-1H-pyrazole-3-carbonyl]-amino}-propionic acid 797(S)-3-(2-Chloro-phenyl)-3-{[1-(2-fluoro- 504.16 1.28 LC11 Aphenyl)-5-((S)-2-hydroxy-3,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}- propionic acid 798(S)-3-(3-Chloro-phenyl)-3-{[1-(2-fluoro- 518.35 1.32 LC11 Aphenyl)-5-((S)-2-hydroxy-2,3,3-trimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}- propionic acid 799(S)-3-{[1-(2-Fluoro-phenyl)-5-((S)-2- 552.32 1.32 LC11 Ahydroxy-2,3,3-trimethyl-butoxy)-1H- pyrazole-3-carbonyl]-amino}-3-(2-trifluoromethyl-phenyl)-propionic acid 800(S)-3-(2,3-Dichloro-phenyl)-3-{[1-(2-fluoro- 538.15 1.31 LC11 Aphenyl)-5-((S)-2-hydroxy-3,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}- propionic acid 801(S)-3-{[1-(2-Fluoro-phenyl)-5-((S)-2- 484.28 1.15 LC11 Ahydroxy-3,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-3-p-tolyl-propionic acid 802(S)-3-{[1-(2-Fluoro-phenyl)-5-(2-hydroxy- 500.26 1.24 LC11 A2,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-3-(3-methoxy-phenyl)- propionic acid 8033-Cyclohexyl-3-{[1-(2-fluoro-phenyl)-5-((S)- 476.32 1.29 LC11 A2-hydroxy-2,3-dimethyl-butoxy)-1H- pyrazole-3-carbonyl]-amino}-propionicacid 804 (S)-3-{[1-(2-Fluoro-phenyl)-5-((R)-2- 484.36 10.25 LC14 Ahydroxy-3,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-3-m-tolyl-propionic acid 805(S)-3-{[5-(3,3-Dimethyl-2-oxo-butoxy)-1-(2- 482.21 1.28 LC11 Afluoro-phenyl)-1H-pyrazole-3-carbonyl]- amino}-3-m-tolyl-propionic acid806 (S)-3-{[1-(2-Fluoro-phenyl)-5-((R)-2- 500.35 1.1 LC11 Ahydroxy-2,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-3-(3-methoxy-phenyl)- propionic acid 807(S)-3-(3-Cyano-phenyl)-3-{[1-(2-fluoro- 495.25 1.22 LC11 Aphenyl)-5-(2-hydroxy-2,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic acid 808(S)-3-(2,6-Difluoro-phenyl)-3-{[1-(2-fluoro- 506.22 1.25 LC11 Aphenyl)-5-(2-hydroxy-2,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic acid 809(S)-3-(3-Chloro-phenyl)-3-{[1-(2-fluoro- 504.31 10.7 LC14 Aphenyl)-5-((S)-2-hydroxy-3,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}- propionic acid 810(S)-3-{[1-(2-Fluoro-phenyl)-5-((S)-2- 514.24 4.54 LC10 Ahydroxy-2,3,3-trimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-3-(2-methoxy- phenyl)-propionic acid 811(S)-3-{[1-(2-Fluoro-phenyl)-5-(2-hydroxy- 500.26 1.26 LC11 A2,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-3-(2-methoxy-phenyl)- propionic acid 812(S)-3-{[1-(2-Fluoro-phenyl)-5-(2-hydroxy- 538.24 1.28 LC11 A2,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-3-(2-trifluoromethyl- phenyl)-propionic acid 8133-Cyclohexyl-3-{[1-(2-fluoro-phenyl)-5-(2- 476.28 1.3 LC11 Ahydroxy-2,3-dimethyl-butoxy)-1H-pyrazole- 3-carbonyl]-amino}-propionicacid 814 3-{[1-(2-Fluoro-phenyl)-5-(2-hydroxy-2,3- 450.25 1.26 LC11 Adimethyl-butoxy)-1H-pyrazole-3-carbonyl]- amino}-5-methyl-hexanoic acid815 (R)-3-(4-Chloro-phenyl)-3-{[1-(2-fluoro- 504.18 1.29 LC11 Aphenyl)-5-(2-hydroxy-3,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic acid 816(S)-3-(2,4-Dichloro-phenyl)-3-{[1-(2-fluoro- 538.2 1.31 LC11 Aphenyl)-5-((R)-2-hydroxy-2,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}- propionic acid 817(S)-3-(2,6-Difluoro-phenyl)-3-{[1-(2-fluoro- 506.28 1.25 LC11 Aphenyl)-5-((S)-2-hydroxy-2,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}- propionic acid 8183-{[1-(2-Fluoro-phenyl)-5-((S)-2-hydroxy- 498.34 1.3 LC11 A2,3,3-trimethyl-butoxy)-1H-pyrazole-3- carbonyl]-amino}-4-phenyl-butyricacid 819 (S)-3-(3-Fluoro-phenyl)-3-{[1-(2-fluoro- 502.35 1.29 LC11 Aphenyl)-5-((S)-2-hydroxy-2,3,3-trimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}- propionic acid 8203-Cyclohexyl-3-{[1-(2-fluoro-phenyl)-5-((R)- 490.36 1.32 LC11 A2-hydroxy-2,3,3-trimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic acid 8213-{[1-(2-Fluoro-phenyl)-5-((R)-2-hydroxy- 484.37 1.12 LC11 A2,3-dimethyl-butoxy)-1H-pyrazole-3- carbonyl]-amino}-4-phenyl-butyricacid 822 (S)-3-{[1-(2-Fluoro-phenyl)-5-((R)-2- 500.34 1.12 LC11 Ahydroxy-2,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-3-(2-methoxy-phenyl)- propionic acid 8233-{[1-(2-Fluoro-phenyl)-5-((R)-2-hydroxy- 450.34 1.13 LC11 B2,3-dimethyl-butoxy)-1H-pyrazole-3- carbonyl]-amino}-5-methyl-hexanoicacid 824 (1-{[1-(2-Fluoro-phenyl)-5-((R)-2-hydroxy- 448.36 1.11 LC11 B2,3-dimethyl-butoxy)-1H-pyrazole-3- carbonyl]-amino}-cyclopentyl)-aceticacid 825 (1-{[1-(2-Fluoro-phenyl)-5-((S)-2-hydroxy- 448.31 1.25 LC11 B2,3-dimethyl-butoxy)-1H-pyrazole-3- carbonyl]-amino}-cyclopentyl)-aceticacid 826 3-{[1-(2-Fluoro-phenyl)-5-((S)-2-hydroxy- 484.3 1.25 LC11 B2,3-dimethyl-butoxy)-1H-pyrazole-3- carbonyl]-amino}-4-phenyl-butyricacid 827 3-{[1-(2-Fluoro-phenyl)-5-((R)-2-hydroxy- 470.33 1.1 LC11 B2,3-dimethyl-butoxy)-1H-pyrazole-3- carbonyl]-amino}-2-phenyl-propionicacid 828 (S)-3-(4-Chloro-phenyl)-3-{[1-(2-fluoro- 504.18 1.29 LC11 Bphenyl)-5-((R)-2-hydroxy-3,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}- propionic acid 8293-{[1-(2-Fluoro-phenyl)-5-(2-hydroxy-2,3- 484.24 1.26 LC11 Bdimethyl-butoxy)-1H-pyrazole-3-carbonyl]- amino}-4-phenyl-butyric acid830 3-{[1-(2-Fluoro-phenyl)-5-((S)-2-hydroxy- 470.32 1.23 LC11 B2,3-dimethyl-butoxy)-1H-pyrazole-3- carbonyl]-amino}-2-phenyl-propionicacid 832 (S)-4-(4-Cyano-phenyl)-3-{[1-(2-fluoro- 523.33 1.25 LC11 Cphenyl)-5-((S)-2-hydroxy-2,3,3-trimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}- butyric acid 833(S)-3-{[1-(2-Fluoro-phenyl)-5-((S)-2- 484.29 1.26 LC11 Chydroxy-2,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-3-o-tolyl-propionic acid 834(S)-4-(4-Cyano-phenyl)-3-{[1-(2-fluoro- 509.31 1.22 LC11 Cphenyl)-5-((S)-2-hydroxy-2,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}- butyric acid 835(S)-3-(2-Fluoro-phenyl)-3-{[1-(2-fluoro- 488.27 1.24 LC11 Aphenyl)-5-((S)-2-hydroxy-2,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}- propionic acid 836(S)-4-(4-Cyano-phenyl)-3-{[1-(2-fluoro- 509.24 1.23 LC11 Cphenyl)-5-(2-hydroxy-2,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-butyric acid 837(S)-3-{[1-(2-Fluoro-phenyl)-5-((S)-2- 484.34 1.25 LC11 Chydroxy-2,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-4-phenyl-butyric acid 838(S)-3-{[1-(2-Fluoro-phenyl)-5-(2-hydroxy- 484.25 1.26 LC11 C2,3-dimethyl-butoxy)-1H-pyrazole-3- carbonyl]-amino}-4-phenyl-butyricacid 839 (S)-3-(2,3-Dichloro-phenyl)-3-{[5-(3,3- 536.13 1.31 LC11 Adimethyl-2-oxo-butoxy)-1-(2-fluoro-phenyl)-1H-pyrazole-3-carbonyl]-amino}-propionic acid 840(S)-3-{[1-(2-Fluoro-phenyl)-5-((S)-2- 500.31 1.23 LC11 Chydroxy-2,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-3-(4-methoxy-phenyl)- propionic acid 841(S)-3-{[1-(2-Fluoro-phenyl)-5-((S)-2- 450.33 1.26 LC11 Chydroxy-2,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-5-methyl-hexanoic acid 842(S)-3-{[1-(2-Fluoro-phenyl)-5-(2-hydroxy- 450.25 1.26 LC112,3-dimethyl-butoxy)-1H-pyrazole-3- carbonyl]-amino}-5-methyl-hexanoicacid 843 (1-{[1-(2-Fluoro-phenyl)-5-(2-hydroxy-2,3- 448.23 1.25 LC11dimethyl-butoxy)-1H-pyrazole-3-carbonyl]- amino}-cyclopentyl)-aceticacid 844 (S)-3-(4-Fluoro-phenyl)-3-{[1-(2-fluoro- 488.21 1.25 LC11phenyl)-5-(2-hydroxy-2,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic acid 845(S)-3-(2,4-Dimethyl-phenyl)-3-{[1-(2-fluoro- 498.27 1.3 LC11phenyl)-5-(2-hydroxy-2,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic acid 846(S)-3-(2-Fluoro-phenyl)-3-{[1-(2-fluoro- 488.22 1.25 LC11phenyl)-5-(2-hydroxy-2,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic acid 847(S)-3-(2,3-Dimethoxy-phenyl)-3-{[1-(2- 530.25 1.25 LC11fluoro-phenyl)-5-(2-hydroxy-2,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}- propionic acid 848(S)-3-{[1-(2-Fluoro-phenyl)-5-(2-hydroxy- 500.25 1.24 LC112,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-3-(4-methoxy-phenyl)- propionic acid 849(S)-3-(2,4-Dichloro-phenyl)-3-{[1-(2-fluoro- 538.2 1.3 LC11 Aphenyl)-5-((S)-2-hydroxy-2,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}- propionic acid 850(S)-3-{[1-(2-Fluoro-phenyl)-5-((R)-2- 500.31 1.1 LC11 Ahydroxy-2,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-3-(4-methoxy-phenyl)- propionic acid 8513-{[1-(2-Fluoro-phenyl)-5-((S)-2-hydroxy- 464.29 4.56 LC112,3,3-trimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-5-methyl-hexanoic acid 852(S)-3-{[1-(2-Fluoro-phenyl)-5-((S)-2- 498.27 4.55 LC11hydroxy-2,3,3-trimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-4-phenyl- butyric acid 853(1-{[1-(2-Fluoro-phenyl)-5-((R)-2-hydroxy- 462.31 1.29 LC112,3,3-trimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-cyclopentyl)-acetic acid 854(S)-3-(2-Fluoro-phenyl)-3-{[1-(2-fluoro- 502.31 1.27 LC11 Bphenyl)-5-((R)-2-hydroxy-2,3,3-trimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}- propionic acid 855(S)-3-(2,3-Dimethoxy-phenyl)-3-{[1-(2- 544.36 1.28 LC11fluoro-phenyl)-5-((R)-2-hydroxy-2,3,3-trimethyl-butoxy)-1H-pyrazole-3-carbonyl]- amino}-propionic acid 856(S)-3-{[1-(2-Fluoro-phenyl)-5-((R)-2- 514.34 1.27 LC11hydroxy-2,3,3-trimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-3-(3-methoxy- phenyl)-propionic acid 857(S)-3-{[1-(2-Fluoro-phenyl)-5-((R)-2- 484.36 10 LC14 Ahydroxy-2,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-3-o-tolyl-propionic acid 858(S)-3-{[1-(2-Fluoro-phenyl)-5-((R)-2- 450.35 1.13 LC11hydroxy-2,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-5-methyl-hexanoic acid 859(S)-3-(2,4-Dimethyl-phenyl)-3-{[1-(2-fluoro- 498.37 1.16 LC11 Aphenyl)-5-((R)-2-hydroxy-2,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}- propionic acid 860(S)-3-{[1-(2-Fluoro-phenyl)-5-((R)-2- 484.34 1.13 LC11 Ahydroxy-2,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-3-p-tolyl-propionic acid 861(S)-3-(2-Chloro-phenyl)-3-{[1-(2-fluoro- 504.27 1.13 LC11 >30phenyl)-5-((R)-2-hydroxy-2,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}- propionic acid 862(S)-3-(2-Fluoro-phenyl)-3-{[1-(2-fluoro- 488.34 1.11 LC11 Bphenyl)-5-((R)-2-hydroxy-2,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}- propionic acid 863(S)-3-{[1-(2-Fluoro-phenyl)-5-((R)-2- 538.31 1.14 LC11hydroxy-2,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-3-(2-trifluoromethyl- phenyl)-propionic acid 864(S)-3-{[1-(2-Fluoro-phenyl)-5-((R)-2- 484.37 1.12 LC11hydroxy-2,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-4-phenyl-butyric acid 865(S)-3-(3-Cyano-phenyl)-3-{[1-(2-fluoro- 495.34 1.08 LC11phenyl)-5-((R)-2-hydroxy-2,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}- propionic acid 866(S)-3-(2,3-Dimethoxy-phenyl)-3-{[1-(2- 530.34 1.12 LC11fluoro-phenyl)-5-((R)-2-hydroxy-2,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]- amino}-propionic acid 867(S)-4-(4-Cyano-phenyl)-3-{[1-(2-fluoro- 509.36 1.09 LC11phenyl)-5-((R)-2-hydroxy-2,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}- butyric acid 868(S)-3-(2,6-Difluoro-phenyl)-3-{[1-(2-fluoro- 506.32 1.12 LC11phenyl)-5-((R)-2-hydroxy-2,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}- propionic acid 869(S)-3-(3-Fluoro-phenyl)-3-{[1-(2-fluoro- 488.33 1.11 LC11phenyl)-5-((R)-2-hydroxy-2,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}- propionic acid 870(S)-3-{[1-(2-Fluoro-phenyl)-5-((S)-2- 484.38 1.13 LC11 Ahydroxy-2,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-3-o-tolyl-propionic acid 8713-{[1-(2-Fluoro-phenyl)-5-((S)-2-hydroxy- 450.35 1.13 LC112,3-dimethyl-butoxy)-1H-pyrazole-3- carbonyl]-amino}-5-methyl-hexanoicacid 872 (S)-3-(4-Fluoro-phenyl)-3-{[1-(2-fluoro- 488.33 1.24 LC11 Bphenyl)-5-((S)-2-hydroxy-2,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}- propionic acid 873(S)-3-(2-Chloro-phenyl)-3-{[1-(2-fluoro- 504.31 1.26 LC11phenyl)-5-((S)-2-hydroxy-2,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}- propionic acid 874(S)-3-(3-Cyano-phenyl)-3-{[1-(2-fluoro- 495.28 1.22 LC11phenyl)-5-((S)-2-hydroxy-2,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}- propionic acid 875(S)-3-{[1-(2-Fluoro-phenyl)-5-((S)-2- 500.31 1.24 LC11hydroxy-2,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-3-(3-methoxy-phenyl)- propionic acid 876(S)-3-(3-Fluoro-phenyl)-3-{[1-(2-fluoro- 488.3 1.25 LC11phenyl)-5-((S)-2-hydroxy-2,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}- propionic acid 877(S)-3-(3-Chloro-phenyl)-3-{[1-(2-fluoro- 504.24 1.27 LC11 Bphenyl)-5-((S)-2-hydroxy-2,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}- propionic acid 878(S)-3-{[1-(2-Fluoro-phenyl)-5-((S)-2- 464.34 1.29 LC11hydroxy-2,3,3-trimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-5-methyl- hexanoic acid 879(1-{[1-(2-Fluoro-phenyl)-5-((S)-2-hydroxy- 462.31 1.29 LC112,3,3-trimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-cyclopentyl)-acetic acid 880(S)-3-(4-Fluoro-phenyl)-3-{[1-(2-fluoro- 502.31 1.29 LC11 Aphenyl)-5-((S)-2-hydroxy-2,3,3-trimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}- propionic acid 881(S)-3-(2,4-Dimethyl-phenyl)-3-{[1-(2-fluoro- 512.37 1.32 LC11phenyl)-5-((S)-2-hydroxy-2,3,3-trimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}- propionic acid 883(S)-3-(2-Fluoro-phenyl)-3-{[1-(2-fluoro- 502.3 1.29 LC11 Aphenyl)-5-((S)-2-hydroxy-2,3,3-trimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}- propionic acid 884(S)-3-(2,3-Dimethoxy-phenyl)-3-{[1-(2- 544.35 1.29 LC11 Afluoro-phenyl)-5-((S)-2-hydroxy-2,3,3-trimethyl-butoxy)-1H-pyrazole-3-carbonyl]- amino}-propionic acid 885(S)-3-{[1-(2-Fluoro-phenyl)-5-((S)-2- 514.24 4.54 LC11hydroxy-2,3,3-trimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-3-(3-methoxy- phenyl)-propionic acid 886(S)-3-{[1-(2-Fluoro-phenyl)-5-((R)-2- 464.36 1.31 LC11hydroxy-2,3,3-trimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-5-methyl- hexanoic acid 888(S)-3-{[1-(2-Fluoro-phenyl)-5-((R)-2- 552.32 1.3 LC11hydroxy-2,3,3-trimethyl-butoxy)-1H- pyrazole-3-carbonyl]-amino}-3-(2-trifluoromethyl-phenyl)-propionic acid 889(S)-4-(4-Cyano-phenyl)-3-{[1-(2-fluoro- 523.33 1.26 LC11phenyl)-5-((R)-2-hydroxy-2,3,3-trimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}- butyric acid 890(S)-3-{[1-(2-Fluoro-phenyl)-5-((R)-2- 514.36 1.26 LC11hydroxy-2,3,3-trimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-3-(4-methoxy- phenyl)-propionic acid 891(S)-3-{[1-(2-Fluoro-phenyl)-5-(2-hydroxy-2- 518.26 4.46 LC10 Aphenyl-propoxy)-1H-pyrazole-3-carbonyl]- amino}-3-o-tolyl-propionic acid892 1-(2-Fluoro-phenyl)-5-methoxy-1H- 488.38 1 LC11pyrazole-3-carboxylic acid {(S)-2-[(pyridin-2-ylmethyl)-carbamoyl]-1-o-tolyl-ethyl}- amide; compound withtrifluoro-acetic acid 893 1-(2-Fluoro-phenyl)-5-methoxy-1H- 451.37 1.13LC11 pyrazole-3-carboxylic acid [(S)-2-(cyclopropylmethyl-carbamoyl)-1-o-tolyl- ethyl]-amide 8941-(2-Fluoro-phenyl)-5-methoxy-1H- 477.36 1.12 LC11 pyrazole-3-carboxylicacid {(S)-2-[(furan-2- ylmethyl)-carbamoyl]-1-o-tolyl-ethyl}-amide 8951-(2-Fluoro-phenyl)-5-methoxy-1H- 482.44 0.91 LC11 pyrazole-3-carboxylicacid [(S)-2-(3- dimethylamino-propylcarbamoyl)-1-o-tolyl- ethyl]-amide;compound with trifluoro- acetic acid 8961-(2-Fluoro-phenyl)-5-methoxy-1H- 467.44 1.17 LC11 pyrazole-3-carboxylicacid [(S)-2-(1-ethyl- propylcarbamoyl)-1-o-tolyl-ethyl]-amide 8971-(2-Fluoro-phenyl)-5-methoxy-1H- 479.05 1.18 LC11 pyrazole-3-carboxylicacid ((S)-2- cyclohexylcarbamoyl-1-o-tolyl-ethyl)-amide 8981-(2-Fluoro-phenyl)-5-methoxy-1H- 467.41 1.04 LC11 pyrazole-3-carboxylicacid [(S)-3-((S)-3- hydroxy-pyrrolidin-1-yl)-3-oxo-1-o-tolyl-propyl]-amide 899 1-(2-Fluoro-phenyl)-5-methoxy-1H- 481.4 4.71 LC10pyrazole-3-carboxylic acid [(S)-1-o-tolyl-2-((R)-1,2,2-trimethyl-propylcarbamoyl)- ethyl]-amide 9001-(2-Fluoro-phenyl)-5-methoxy-1H- 467.36 1.04 LC11 pyrazole-3-carboxylicacid [(S)-3-((R)-3- hydroxy-pyrrolidin-1-yl)-3-oxo-1-o-tolyl-propyl]-amide 901 1-(2-Fluoro-phenyl)-5-methoxy-1H- 453.25 1.15 LC11pyrazole-3-carboxylic acid [(S)-2-((S)-sec-butylcarbamoyl)-1-o-tolyl-ethyl]-amide 9021-(2-Fluoro-phenyl)-5-methoxy-1H- 481.25 1.07 LC11 pyrazole-3-carboxylicacid [(S)-3-((S)-3- hydroxy-piperidin-1-yl)-3-oxo-1-o-tolyl-propyl]-amide 903 1-(2-Fluoro-phenyl)-5-methoxy-1H- 468.23 1.02 LC11pyrazole-3-carboxylic acid [(S)-2-(carbamoylmethyl-methyl-carbamoyl)-1-o- tolyl-ethyl]-amide 9041-(2-Fluoro-phenyl)-5-methoxy-1H- 465.25 1.16 LC11 pyrazole-3-carboxylicacid [(S)-2-((R)-1- cyclopropyl-ethylcarbamoyl)-1-o-tolyl- ethyl]-amide905 1-(2-Fluoro-phenyl)-5-methoxy-1H- 465.25 1.16 LC11pyrazole-3-carboxylic acid [(S)-2-((S)-1-cyclopropyl-ethylcarbamoyl)-1-o-tolyl- ethyl]-amide 9061-(2-Fluoro-phenyl)-5-methoxy-1H- 451.39 1.13 LC11 pyrazole-3-carboxylicacid ((S)-2- cyclobutylcarbamoyl-1-o-tolyl-ethyl)-amide 9071-(2-Fluoro-phenyl)-5-methoxy-1H- 488.42 0.95 LC11 pyrazole-3-carboxylicacid {(S)-2-[(pyridin- 3-ylmethyl)-carbamoyl]-1-o-tolyl-ethyl}- amide;compound with trifluoro-acetic acid 9081-(2-Fluoro-phenyl)-5-methoxy-1H- 465.43 1.16 LC11 pyrazole-3-carboxylicacid ((S)-2- cyclopentylcarbamoyl-1-o-tolyl-ethyl)- amide 9091-(2-Fluoro-phenyl)-5-methoxy-1H- 469.4 1.11 LC11 pyrazole-3-carboxylicacid [(S)-2-(2- methoxy-1-methyl-ethylcarbamoyl)-1-o- tolyl-ethyl]-amide910 1-(2-Fluoro-phenyl)-5-methoxy-1H- 461.2 1.11 LC11pyrazole-3-carboxylic acid [(S)-2-(2,2-difluoro-ethylcarbamoyl)-1-o-tolyl-ethyl]- amide 9111-(2-Fluoro-phenyl)-5-methoxy-1H- 479.18 1.14 LC11 pyrazole-3-carboxylicacid [(S)-1-o-tolyl-2- (2,2,2-trifluoro-ethylcarbamoyl)-ethyl]- amide912 1-(2-Fluoro-phenyl)-5-methoxy-1H- 465.25 1.16 LC11pyrazole-3-carboxylic acid [(S)-2-(2-cyclopropyl-ethylcarbamoyl)-1-o-tolyl- ethyl]-amide 9131-(2-Fluoro-phenyl)-5-methoxy-1H- 489.23 1.02 LC11 pyrazole-3-carboxylicacid {(S)-2- [(pyrimidin-5-ylmethyl)-carbamoyl]-1-o- tolyl-ethyl}-amide914 1-(2-Fluoro-phenyl)-5-methoxy-1H- 453.25 1.15 LC11pyrazole-3-carboxylic acid ((S)-2- butylcarbamoyl-1-o-tolyl-ethyl)-amide915 1-(2-Fluoro-phenyl)-5-methoxy-1H- 477.22 1.12 LC11pyrazole-3-carboxylic acid {(S)-2-[(furan-3-ylmethyl)-carbamoyl]-1-o-tolyl-ethyl}-amide 9161-(2-Fluoro-phenyl)-5-methoxy-1H- 488.41 0.92 LC11 Cpyrazole-3-carboxylic acid {(S)-2-[(pyridin-4-ylmethyl)-carbamoyl]-1-o-tolyl-ethyl}- amide; compound withtrifluoro-acetic acid 917 1-(2-Fluoro-phenyl)-5-methoxy-1H- 467.44 1.19LC11 C pyrazole-3-carboxylic acid [(S)-2-(1,1-dimethyl-propylcarbamoyl)-1-o-tolyl-ethyl]- amide 9181-(2-Fluoro-phenyl)-5-methoxy-1H- 453.25 1.15 LC11 Cpyrazole-3-carboxylic acid [(S)-2-((R)-sec-butylcarbamoyl)-1-o-tolyl-ethyl]-amide 9191-(2-Fluoro-phenyl)-5-methoxy-1H- 453.37 1.15 LC11 Cpyrazole-3-carboxylic acid ((S)-2-isobutylcarbamoyl-1-o-tolyl-ethyl)-amide 9201-(2-Fluoro-phenyl)-5-methoxy-1H- 481.51 1.2 LC11 Cpyrazole-3-carboxylic acid [(S)-1-o-tolyl-2-((S)-1,2,2-trimethyl-propylcarbamoyl)- ethyl]-amide 9211-(2-Fluoro-phenyl)-5-methoxy-1H- 483.26 1.13 LC11 Cpyrazole-3-carboxylic acid [(S)-2-(1-methoxymethyl-propylcarbamoyl)-1-o-tolyl- ethyl]-amide 9221-(2-Fluoro-phenyl)-5-methoxy-1H- 453.25 1.17 LC11 Cpyrazole-3-carboxylic acid ((S)-2-tert-butylcarbamoyl-1-o-tolyl-ethyl)-amide 9231-(2-Fluoro-phenyl)-5-methoxy-1H- 477.23 1.07 LC11 Cpyrazole-3-carboxylic acid [(S)-2-(5-methyl-1H-pyrazol-3-ylcarbamoyl)-1-o- tolyl-ethyl]-amide 9241-(2-Fluoro-phenyl)-5-methoxy-1H- 467.38 1.08 LC11 Apyrazole-3-carboxylic acid [(S)-2-(2,2-dimethyl-propylcarbamoyl)-1-o-tolyl-ethyl]- amide 9251-(2-Fluoro-phenyl)-5-methoxy-1H- 483.41 1.09 LC11 Cpyrazole-3-carboxylic acid [(S)-2-(3-hydroxy-2,2-dimethyl-propylcarbamoyl)-1- o-tolyl-ethyl]-amide 9261-(2-Fluoro-phenyl)-5-methoxy-1H- 436.2 1.07 LC11 Cpyrazole-3-carboxylic acid [(S)-2-(cyanomethyl-carbamoyl)-1-o-tolyl-ethyl]- amide 9271-(2-Fluoro-phenyl)-5-methoxy-1H- 483.26 1.09 LC11 Bpyrazole-3-carboxylic acid [(S)-2-((R)-1-hydroxymethyl-2-methyl-propylcarbamoyl)- 1-o-tolyl-ethyl]-amide 9281-(2-Fluoro-phenyl)-5-methoxy-1H- 479.22 1.02 LC11 Bpyrazole-3-carboxylic acid {(S)-2-[(1H-tetrazol-5-ylmethyl)-carbamoyl]-1-o-tolyl- ethyl}-amide 9291-(2-Fluoro-phenyl)-5-methoxy-1H- 439.39 1.12 LC11 Bpyrazole-3-carboxylic acid ((S)-2-isopropylcarbamoyl-1-o-tolyl-ethyl)-amide 9301-(2-Fluoro-phenyl)-5-methoxy-1H- 477.23 1.08 LC11 Bpyrazole-3-carboxylic acid [(S)-2-(1-methyl-1H-pyrazol-3-ylcarbamoyl)-1-o- tolyl-ethyl]-amide 9311-(2-Fluoro-phenyl)-5-methoxy-1H- 480.24 1.01 LC11 Cpyrazole-3-carboxylic acid [(S)-2-(2-oxo-pyrrolidin-3-ylcarbamoyl)-1-o-tolyl-ethyl]- amide 9321-(2-Fluoro-phenyl)-5-methoxy-1H- 478.36 1.13 LC11 Bpyrazole-3-carboxylic acid [(S)-2-(5-methyl-isoxazol-3-ylcarbamoyl)-1-o-tolyl- ethyl]-amide 9331-(2-Fluoro-phenyl)-5-methoxy-1H- 437.29 1.08 LC11 Apyrazole-3-carboxylic acid ((S)-2-cyclopropylcarbamoyl-1-o-tolyl-ethyl)- amide 9341-(2-Fluoro-phenyl)-5-methoxy-1H- 478.22 1.08 LC11 Apyrazole-3-carboxylic acid {(S)-2-[(isoxazol-5-ylmethyl)-carbamoyl]-1-o-tolyl- ethyl}-amide 9351-(2-Fluoro-phenyl)-5-methoxy-1H- 455.37 1.08 LC11 Apyrazole-3-carboxylic acid [(S)-2-(2-methoxy-ethylcarbamoyl)-1-o-tolyl-ethyl]- amide 9361-(2-Fluoro-phenyl)-5-methoxy-1H- 483.43 1.09 LC11 Apyrazole-3-carboxylic acid [(S)-2-((S)-1-hydroxymethyl-2-methyl-propylcarbamoyl)- 1-o-tolyl-ethyl]-amide 9371-(2-Fluoro-phenyl)-5-methoxy-1H- 469.24 1.1 LC11 Apyrazole-3-carboxylic acid [(S)-2-((S)-2-methoxy-1-methyl-ethylcarbamoyl)-1-o- tolyl-ethyl]-amide 9381-(2-Fluoro-phenyl)-5-methoxy-1H- 481.25 1.1 LC11 Apyrazole-3-carboxylic acid ((S)-2-{[(S)-1-(tetrahydro-furan-2-yl)methyl]-carbamoyl}- 1-o-tolyl-ethyl)-amide 9391-(2-Fluoro-phenyl)-5-methoxy-1H- 467.23 1.09 LC11 Apyrazole-3-carboxylic acid [(S)-2-((R)-1,2-dimethyl-propylcarbamoyl)-1-o-tolyl-ethyl]- amide (1) Mass spectroscopiccharacterization; observed mass number of the ion [(M + H)⁺], unlessspecified otherwise (2) Cathepsin A inhibitory activity determined inthe pharmacological test “Cathepsin A inhibitory activity” describedbelow. “A” means an IC₅₀ value of less than 0.1 μM, “B” means an IC₅₀value between 0.1 μM and 1 μM, “C” means an IC₅₀ value between 1 μM and30 μM. (3) The two compounds of examples 745 and 746; the two compoundsof examples 747 and 748; the two compounds of examples 753 and 754; thetwo compounds of examples 758 and 759; the two compounds of examples 760and 761; and the two compounds of examples 763 and 764 each are twodiastereomeric compounds, one of them being the diastereomer with Rconfiguration in the alcohol moiety and the other of them being thediastereomer with S configuration in the alcohol moiety (thestereochemistry in the alcohol moiety was not determined; it wasarbitrarily assigned R configuration in the first diastereomer elutedfrom the chromatography column and S configuration in the seconddiastereomer eluted from the chromatography column).

Exemplary ¹H-NMR Data of Example Compounds EXAMPLE 3

δ (ppm)=2.75 (dd, 1H); 2.92 (dd, 1H); 3.75 (s, 3H); 5.35 (q, 1H); 5.85(s, 1H); 6.85 (d, 2H); 7.3 (m, 3H); 7.5 (m, 2H); 7.75 (d, 2H); 8.5 (d,1H)

EXAMPLE 7

δ (ppm)=1.25 (s, 9H); 2.0 (s, 3H); 2.3 (s, 3H); 2.75 (dd, 1H); 2.9 (dd,1H); 5.35 (q, 1H); 5.8 (s, 1H); 6.7 (m, 1H); 7.05-7.3 (m, 6H); 8.5 (d,1H)

EXAMPLE 129

δ (ppm)=2.4 (s, 3H); 2.7 (dd, 1H); 2.9 (dd, 1H); 3.9 (s, 3H); 5.6 (q,1H); 6.2 (s, 1H); 7.1 (m, 3H); 7.4 (m, 1H); 7.5 (m, 2H); 7.6 (m, 2H);8.65 (d, 1H)

EXAMPLE 523

δ (ppm)=2.35 (s, 3H); 2.75 (dd, 1H); 2.9 (dd, 1H); 5.6 (q, 1H); 5.85 (s,1H); 7.0 (t, 1H); 7.2 (q, 1H); 7.35 (m, 3H); 7.8 (m, 2H); 8.65 (d, 1H)

EXAMPLE 524

δ (ppm)=2.7 (dd, 1H); 2.9 (dd, 1H); 5.7 (m, 1H); 5.85 (s, 1H); 7.25 (m,1H); 7.3-7.4 (m, 3H); 7.45 (m, 1H); 7.8 (m, 2H); 8.75 (d, 2H)

EXAMPLE 534

δ (ppm)=2.4 (s, 3H); 2.7 (dd, 1H); 2.9 (dd, 1H); 5.6 (s, 1H); 6.25 (s,1H); 7.1 (m, 3H); 7.35 (m, 1H); 7.5 (m, 3H); 7.7 (d, 2H); 8.65 (d, 1H)

EXAMPLE 548

δ (ppm)=2.7 (dd, 1H); 2.85 (dd, 1H); 3.9 (s, 3H); 5.7 (m, 1H); 5.9 (s,1H); 7.2 (d, 1H); 7.35 (t, 1H); 7.5 (t, 2H); 7.6 (d, 1H); 7.65 (s, 1H);7.8 (d, 2H); 8.6 (d, 1H)

EXAMPLE 564

δ (ppm)=2.3 (s, 3H); 2.7 (dd, 1H); 2.9 (dd, 1H); 5.6 (m, 1H); 5.85 (s,1H); 7.0 (m, 2H); 7.35 (m, 2H); 7.5 (m, 2H); 7.8 (m, 2H); 8.6 (d, 1H)

EXAMPLE 585

δ (ppm)=2.85 (dd, 1H); 3.0 (dd, 1H); 5.4 (q, 1H); 5.8 (s, 1H); 7.2-7.6(m, 12H); 8.6 (d, 1H)

EXAMPLE 597

δ (ppm)=2.85 (dd, 1H); 3.0 (dd, 1H); 3.95 (s, 3H); 5.5 (q, 1H); 6.25 (s,1H); 7.3-8.6 (several m, 13H); 8.75 (d, 1H)

EXAMPLE 603

δ (ppm)=2.8 (dd, 1H); 3.0 (dd, 1H); 3.2 (s, 3H); 5.45 (q, 1H); 5.8 (s,1H); 7.3 (t, 1H); 7.4 (t, 1H); 7.55 (m, 2H); 7.6 (d, 2H); 7.85 (d, 2H);8.75 (d, 1H)

EXAMPLE 607

δ (ppm)=2.4 (s, 3H); 2.6 (dd, 1H); 2.8 (dd, 1H); 5.6 (m, H); 5.8 (s,1H); 7.1 (m, 3H); 7.4 (m, 1H); 7.6 (d, 1H); 7.8 (m, 1H); 7.9 (m, 1H);8.1 (m, 1H); 8.6 (d, 1H)

EXAMPLE 618

δ (ppm)=1.05 (t, 3H); 2.4 (s, 3H); 2.8 (dd, 1H); 2.95 (dd, 1H); 3.9 (s,3H); 4.0 (q, 2H); 5.5 (q, 1H); 6.2 (s, 1H); 7.1 (m, 3H); 7.35 (m, 1H);7.45 (m, 2H); 7.55 (m, 2H); 8.7 (d, 1H)

EXAMPLE 672

δ (ppm)=2.4 (s, 3H); 2.7 (dd, 1H); 2.9 (dd, 1H); 3.7 (s, 3H); 3.9 (s,3H); 5.6 (q, 1H); 6.2 (s, 1H); 6.7 (m, 2H); 7.35 (m, 2H); 7.45 (m, 1H);7.55 (m, 2H); 8.55 (d, 1H)

EXAMPLE 680

δ (ppm)=3.0 (m, 2H); 3.9 (s, 3H); 5.8 (m, 1H); 6.2 (s, 1H); 7.45 (m,1H); 7.55 (m, 2H); 7.5-7.7 (m, 4H); 7.8 (m, 1H); 8.9 (d, 1H)

EXAMPLE 682

δ (ppm)=2.2 (s, 3H); 2.3 (s, 3H); 2.65 (dd, 1H); 2.9 (dd, 1H); 3.9 (s,3H); 5.7 (q, 1H); 6.2 (s, 1H); 7.0 (m, 2H); 7.3 (m, 1H); 7.35 (m, 1H);7.45 (m, 1H); 7.55 (m, 2H); 8.6 (d, 1H)

EXAMPLE 684

δ (ppm)=0.3 (m, 2H); 0.5 (m, 2H); 1.2 (m, 1H); 2.3 (s, 3H); 2.75 (dd,1H); 2.9 (dd, 1H); 4.0 (d, 2H); 5.6 (q, 1H); 6.2 (s, 1H); 7.0 (m, 1H);7.2 (m, 1H); 7.3 (m, 1H); 7.35 (m, 1H); 7.45 (m, 1H); 7.55 (m, 2H); 8.75(d, 1H)

EXAMPLE 690

δ (ppm)=0.3 (m, 2H); 0.5 (m, 2H); 1.2 (m, 1H); 2.25 (s, 3H); 2.7 (dd,1H); 2.9 (dd, 1H); 4.0 (d, 2H); 5.3 (q, 1H); 6.2 (s, 1H); 7.0 (m, 1H);7.2 (m, 2H); 7.35 (m, 1H); 7.45 (m, 1H); 7.55 (m, 2H); 8.6 (d, 2H)

EXAMPLE 700

δ (ppm)=1.1 (s, 9H); 2.4 (s, 3H); 2.7 (dd, 1H); 2.9 (dd, 1H); 5.25 (s,2H); 5.6 (q, 1H); 6.1 (s, 1H); 7.1 (m, 3H); 7.35 (m, 1H); 7.45 (m, 2H);7.55-7.7 (m, 2H); 8.7 (d, 1H)

EXAMPLE 744

δ (ppm)=0.8 (s, 9H); 2.45 (s, 3H); 2.7 (m, 1H); 2.9 (m, 1H); 3.9 (m,1H); 4.2 (m, 1H); 4.9 (m, 1H); 5.6 (q, 1H); 6.2 (s, 1H); 7.1 (m, 3H);7.35 (m, 1H); 7.45 (m, 2H); 7.55 (m, 2H); 8.65 (d, 1H)

EXAMPLE 751

δ (ppm)=1.05 (s, 6H); 2.65 (dd, 1H); 2.9 (dd, 1H); 3.9 (s, 2H); 5.7 (m,1H); 6.2 (s, 1H); 7.3-7.6 (m, 7H); 8.8 (d, 1H)

EXAMPLE 757

δ (ppm)=0.1-0.25 (m, 3H); 0.3 (m, 1H); 0.7 (m, 1H); 1.05 (s, 3H); 2.4(s, 3H); 2.7 (dd, 1H); 2.9 (m, 1H); 3.9 (m, 2H); 5.6 (m, 1H); 6.2 (s,1H); 7.1 (m, 3H); 7.35 (m, 1H); 7.45 (m, 2H); 7.6 (m, 2H); 8.6 (d, 1H)

EXAMPLE 758

δ (ppm)=0.8 (s, 9H); 1.05 (s, 3H); 2.65 (dd, 1H); 2.9 (dd, 1H); 3.95 (d,1H); 4.1 (d, 1H); 5.75 (m, 1H); 6.2 (s, 1H); 7.3-7.6 (m, 8H); 8.8 (d,1H)

EXAMPLE 759

δ (ppm)=0.8 (s, 9H); 1.0 (s, 3H); 2.65 (dd, 1H); 2.9 (m, 1H); 4.0 (d,1H); 4.1 (d, 1H); 5.75 (m, 1H); 6.25 (s, 1H); 7.25-7.6 (m, 8H); 8.8 (d,1H)

EXAMPLE 762

δ (ppm)=0.7 (t, 6H); 1.3 (m, 4H); 2.65 (dd, 1H); 2.9 (dd, 1H); 3.9 (s,2H); 5.7 (m, 1H); 6.2 (s, 1H); 7.3-7.6 (m, 7H); 8.85 (d, 1H)

Pharmacological Tests

a) Cathepsin A Inhibitory Activity

Recombinant human cathepsin A (residues 29-480, with a C-terminal 10-Histag; R&D Systems, #1049-SE) was proteolytically activated withrecombinant human cathepsin L (R&D Systems, #952-CY). Briefly, cathepsinA was incubated at 10 μg/ml with cathepsin L at 1 μg/ml in activationbuffer (25 mM 2-(morpholin-4-yl)-ethanesulfonic acid (MES), pH 6.0,containing 5 mM dithiothreitol (DTT)) for 15 min at 37° C. Cathepsin Lactivity was then stopped by the addition of the cysteine proteaseinhibitor E-64 (N-(trans-epoxysuccinyl)-L-leucine-4-guanidinobutylamide;Sigma-Aldrich, #E3132; dissolved in activation buffer/DMSO) to a finalconcentration of 10 μM.

The activated cathepsin A was diluted in assay buffer (25 mM MES, pH5.5, containing 5 mM DTT) and mixed with the test compound (dissolved inassay buffer containing (v/v) 3% DMSO) or, in the control experiments,with the vehicle in a multiple assay plate. After incubation for 15 minat room temperature, as substrate then bradykinin carrying anN-terminal®Bodipy FL(4,4-difluoro-5,7-dimethyl-4-bora-3a,4a-diaza-s-indacene-3-propionyl)label (JPT Peptide Technologies GmbH; dissolved in assay buffer) wasadded to the mixture. The final concentration of cathepsin A was 833ng/ml and the final concentration of labeled bradykinin 2 μM. Afterincubation for 15 min at room temperature the reaction was stopped bythe addition of stop buffer (130 mM2-(4-(2-hydroxy-ethyl)-piperazin-1-yl)-ethanesulfonic acid, pH 7.4,containing (v/v) 0.013% Triton X-100, 0.13% Coating Reagent 3 (CaliperLife Sciences), 6.5% DMSO and 20 μM ebelactone B (Sigma, # E0886)).

Uncleaved substrate and product were then separated by a microfluidiccapillary electrophoresis on a LabChip® 3000 Drug Discovery System(12-Sipper-Chip; Caliper Life Sciences) and quantified by determinationof the respective peak areas. Substrate turnover was calculated bydividing product peak area by the sum of substrate and product peakareas, and the enzyme activity and the inhibitory effect of the testcompound thus quantified. From the percentage of inhibition of cathepsinA activity observed with the test compound at several concentrations,the inhibitory concentration IC₅₀, i.e. the concentration which effects50% inhibition of enzyme activity was, calculated. IC₅₀ values ofvarious example compounds are given in Table 1, wherein “A” means anIC₅₀ value of less than 0.1 μM, “B” means an IC₅₀ value between 0.1 μMand 1 μM, and “C” means an IC₅₀ value between 1 μM and 30 μM.

B) In Vivo Antihypertrophic and Renoprotective Activity

The in vivo pharmacological activity of the compounds of the inventioncan be investigated, for example, in the model of DOCA-salt sensitiverats with unilateral nephrectomy. Briefly, in this model unilateralnephrectomy of the left kidney (UNX) is performed on Sprague Dawley ratsof 150 g to 200 g of body weight. After the operation as well as at thebeginning of each of the following weeks 30 mg/kg of body weight of DOCA(desoxycorticosterone acetate) are administered to the rats bysubcutaneous injection. The nephrectomized rats treated with DOCA aresupplied with drinking water containing 1% of sodium chloride (UNX/DOCArats). The UNX/DOCA rats develop high blood pressure, endothelialdysfunction, myocardial hypertrophy and fibrosis as well as renaldysfunction. In the test group (UNX/DOCA Test) and the placebo group(UNX/DOCA Placebo), which consist of randomized UNX/DOCA rats, the ratsare treated orally by gavage in two part administrations at 6 a.m. and 6p.m. with the daily dose of the test compound (for example 10 mg/kg ofbody weight dissolved in vehicle) or with vehicle only, respectively. Ina control group (control), which consists of animals which have not beensubjected to UNX and DOCA administration, the animals receive normaldrinking water and are treated with vehicle only. After five weeks oftreatment, systolic blood pressure (SBP) and heart rate (HR) aremeasured non-invasively via the tail cuff method. For determination ofalbuminuria and creatinine, 24 h urine is collected on metabolic cages.Endothelial function is assessed in excised rings of the thoracic aortaas described previously (W. Linz et al., JRAAS (Journal of therenin-angiotensin-aldosterone system) 7 (2006), 155-161). As a measureof myocardial hypertrophy and fibrosis, heart weight, left ventricularweight and the relation of hydroxyproline and proline are determined inexcised hearts.

TABLE 2 Cathepsin A inhibitory activity IC₅₀ Ex- CATH-A ample CompoundName IC₅₀ (μM) 129(S)-3-{[1-(2-Fluoro-phenyl)-5-methoxy-1H-pyrazole-3-carbonyl]- 0.041249amino}-3-o-tolyl-propionic acid 135(S)-3-{[1-(2-Chloro-phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- 0.210567amino}-3-p-tolyl-propionic acid 2213-{[1-(2-Chloro-phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- 0.322137amino}-3-(2-fluoro-3-trifluoromethyl-phenyl)-propionic acid 3853-{[1-(2,4-Difluoro-phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- 0.060742amino}-3-(2-fluoro-3-trifluoromethyl-phenyl)-propionic acid 4183-{[1-(3-Chloro-phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- 5.287222amino}-3-(2-fluoro-3-trifluoromethyl-phenyl)-propionic acid 4413-(2-Fluoro-6-methoxy-phenyl)-3-[(5-hydroxy-1-phenyl-1H- 0.513333pyrazole-3-carbonyl)-amino]-propionic acid 4433-(5-Fluoro-2-trifluoromethyl-phenyl)-3-[(5-hydroxy-1-phenyl- 0.2204641H-pyrazole-3-carbonyl)-amino]-propionic acid 4443-(2,5-Dichloro-phenyl)-3-[(5-hydroxy-1-phenyl-1H-pyrazole-3- 0.083052carbonyl)-amino]-propionic acid 445(S)-3-[(5-Hydroxy-1-phenyl-1H-pyrazole-3-carbonyl)-amino]-3- 0.129975p-tolyl-propionic acid 446(S)-3-(2-Chloro-phenyl)-3-[(5-hydroxy-1-phenyl-1H-pyrazole-3- 0.120455carbonyl)-amino]-propionic acid 4473-{[1-(2,4-Difluoro-phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- 0.114465amino}-3-(3-fluoro-2-methyl-phenyl)-propionic acid 4483-(2-Chloro-4-dimethylamino-phenyl)-3-{[1-(2,4-difluoro-phenyl)-0.883729 5-hydroxy-1H-pyrazole-3-carbonyl]-amino}-propionic acid 4493-{[1-(2,4-Difluoro-phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- 0.175869amino}-3-(2-fluoro-6-methoxy-phenyl)-propionic acid 4503-(2,2-Difluoro-benzo[1,3]dioxol-4-yl)-3-{[1-(2,4-difluoro-phenyl)-0.408735 5-hydroxy-1H-pyrazole-3-carbonyl]-amino}-propionic acid 4513-(2,5-Difluoro-phenyl)-3-{[1-(2,4-difluoro-phenyl)-5-hydroxy-1H-0.232875 pyrazole-3-carbonyl]-amino}-propionic acid 4523-{[1-(2,4-Difluoro-phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- 0.138677amino}-3-(5-fluoro-2-trifluoromethyl-phenyl)-propionic acid 4533-{[1-(2,4-Difluoro-phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- 0.248853amino}-3-(5-fluoro-2-methoxy-phenyl)-propionic acid 454(S)-3-{[1-(2,4-Difluoro-phenyl)-5-hydroxy-1H-pyrazole-3- 0.185593carbonyl]-amino}-3-p-tolyl-propionic acid 4553-{[1-(2-Chloro-phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- 0.154288amino}-3-(3-fluoro-2-methyl-phenyl)-propionic acid 4573-{[1-(2-Chloro-phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- 0.170335amino}-3-(2-fluoro-6-methoxy-phenyl)-propionic acid 4583-(2-Chloro-5-fluoro-phenyl)-3-{[1-(2-chloro-phenyl)-5-hydroxy- 0.22271H-pyrazole-3-carbonyl]-amino}-propionic acid 4593-{[1-(2-Chloro-phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- 0.128099amino}-3-(2,5-difluoro-phenyl)-propionic acid 4603-{[1-(2-Chloro-phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- 0.117776amino}-3-(5-fluoro-2-trifluoromethyl-phenyl)-propionic acid 4613-{[1-(2-Chloro-phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- 0.150702amino}-3-(5-fluoro-2-methyl-phenyl)-propionic acid 4623-{[1-(2-Chloro-phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- 0.080429amino}-3-(2,5-dichloro-phenyl)-propionic acid 4633-(2-Chloro-4-dimethylamino-phenyl)-3-{[1-(3-chloro-phenyl)-5- 11.052896hydroxy-1H-pyrazole-3-carbonyl]-amino}-propionic acid 4643-{[1-(3-Chloro-phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- 0.27418amino}-3-(2,2-difluoro-benzo[1,3]dioxol-4-yl)-propionic acid 4653-{[1-(3-Chloro-phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- 0.738351amino}-3-(2,5-difluoro-phenyl)-propionic acid 4663-{[1-(3-Chloro-phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- 0.561884amino}-3-(5-fluoro-2-trifluoromethyl-phenyl)-propionic acid 4673-{[1-(3-Chloro-phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- 2.24854amino}-3-(2-trifluoromethylsulfanyl-phenyl)-propionic acid 4683-{[1-(4-Chloro-phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- 0.279829amino}-3-(3-fluoro-2-methyl-phenyl)-propionic acid 4693-{[1-(4-Chloro-phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- 0.860051amino}-3-(2-fluoro-6-methoxy-phenyl)-propionic acid 4703-(2-Chloro-5-fluoro-phenyl)-3-{[1-(4-chloro-phenyl)-5-hydroxy- 0.3983631H-pyrazole-3-carbonyl]-amino}-propionic acid 4713-{[1-(4-Chloro-phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- 0.486287amino}-3-(2,2-difluoro-benzo[1,3]dioxol-4-yl)-propionic acid 4723-{[1-(4-Chloro-phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- 4.087942amino}-3-(2,5-difluoro-phenyl)-propionic acid 4733-{[1-(4-Chloro-phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- 1.726107amino}-3-(5-fluoro-2-trifluoromethyl-phenyl)-propionic acid 474(S)-3-(2-Chloro-phenyl)-3-{[1-(4-chloro-phenyl)-5-hydroxy-1H- 0.206959pyrazole-3-carbonyl]-amino}-propionic acid 4753-(2-Chloro-5-fluoro-phenyl)-3-{[1-(2-fluoro-phenyl)-5-hydroxy- 0.1366961H-pyrazole-3-carbonyl]-amino}-propionic acid 4923-(5-Fluoro-2-methyl-phenyl)-3-{[1-(4-fluoro-phenyl)-5-hydroxy- 0.1752591H-pyrazole-3-carbonyl]-amino}-propionic acid 4933-(2,5-Dichloro-phenyl)-3-{[1-(4-fluoro-phenyl)-5-hydroxy-1H- 0.245667pyrazole-3-carbonyl]-amino}-propionic acid 4943-(3-Fluoro-2-methyl-phenyl)-3-[(5-hydroxy-1-phenyl-1H- 0.142178pyrazole-3-carbonyl)-amino]-propionic acid 4953-(2-Chloro-5-fluoro-phenyl)-3-[(5-hydroxy-1-phenyl-1H- 0.213013pyrazole-3-carbonyl)-amino]-propionic acid 4963-(2,2-Difluoro-benzo[1,3]dioxol-4-yl)-3-[(5-hydroxy-1-phenyl- 0.1665221H-pyrazole-3-carbonyl)-amino]-propionic acid 4973-(5-Fluoro-2-methyl-phenyl)-3-[(5-hydroxy-1-phenyl-1H- 0.145434pyrazole-3-carbonyl)-amino]-propionic acid 4983-(5-Fluoro-2-methoxy-phenyl)-3-[(5-hydroxy-1-phenyl-1H- 0.142545pyrazole-3-carbonyl)-amino]-propionic acid 4993-[(5-Hydroxy-1-phenyl-1H-pyrazole-3-carbonyl)-amino]-3-(4- 0.147004pyridin-2-yl-phenyl)-propionic acid; compound with trifluoro- aceticacid 500 3-(2,5-Dichloro-phenyl)-3-{[1-(2,4-difluoro-phenyl)-5-hydroxy-0.086296 1H-pyrazole-3-carbonyl]-amino}-propionic acid 502(S)-3-(2-Chloro-phenyl)-3-{[1-(2,4-difluoro-phenyl)-5-hydroxy- 0.1161381H-pyrazole-3-carbonyl]-amino}-propionic acid 5033-{[1-(2-Chloro-phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- 0.391391amino}-3-(2,2-difluoro-benzo[1,3]dioxol-4-yl)-propionic acid 5043-{[1-(2-Chloro-phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- 0.123363amino}-3-(5-fluoro-2-methoxy-phenyl)-propionic acid 5053-{[1-(2-Chloro-phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- 29.754902amino}-3-(4-morpholin-4-yl-phenyl)-propionic acid 5063-{[1-(2-Chloro-phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- 0.05236amino}-3-(4-pyridin-2-yl-phenyl)-propionic acid 507(S)-3-(2-Chloro-phenyl)-3-{[1-(2-chloro-phenyl)-5-hydroxy-1H- 0.160998pyrazole-3-carbonyl]-amino}-propionic acid 5083-{[1-(3-Chloro-phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- 0.136863amino}-3-(3-fluoro-2-methyl-phenyl)-propionic acid 5093-(2-Chloro-5-fluoro-phenyl)-3-{[1-(3-chloro-phenyl)-5-hydroxy- 0.1003691H-pyrazole-3-carbonyl]-amino}-propionic acid 5103-{[1-(3-Chloro-phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- 0.175019amino}-3-(5-fluoro-2-methyl-phenyl)-propionic acid 5113-{[1-(3-Chloro-phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- 0.101707amino}-3-(2,5-dichloro-phenyl)-propionic acid 512(S)-3-{[1-(3-Chloro-phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- 0.155051amino}-3-p-tolyl-propionic acid 5133-{[1-(3-Chloro-phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- 0.194548amino}-3-(4-pyridin-2-yl-phenyl)-propionic acid 514(S)-3-(2-Chloro-phenyl)-3-{[1-(3-chloro-phenyl)-5-hydroxy-1H- 0.303517pyrazole-3-carbonyl]-amino}-propionic acid 5153-{[1-(4-Chloro-phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- 0.238394amino}-3-(4-pyridin-2-yl-phenyl)-propionic acid 5163-(3-Fluoro-2-methyl-phenyl)-3-{[1-(2-fluoro-phenyl)-5-hydroxy- 0.101911H-pyrazole-3-carbonyl]-amino}-propionic acid 5253-(5-Fluoro-2-methoxy-phenyl)-3-{[1-(4-fluoro-phenyl)-5- 1.505027hydroxy-1H-pyrazole-3-carbonyl]-amino}-propionic acid 526(S)-3-{[1-(4-Fluoro-phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- 0.357948amino}-3-p-tolyl-propionic acid 5273-{[1-(4-Fluoro-phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- 0.152264amino}-3-(4-pyridin-2-yl-phenyl)-propionic acid 528(S)-3-(2-Chloro-phenyl)-3-{[1-(4-fluoro-phenyl)-5-hydroxy-1H- 0.413048pyrazole-3-carbonyl]-amino}-propionic acid 5453-[(5-Hydroxy-1-phenyl-1H-pyrazole-3-carbonyl)-amino]-3-(3- 1.112898methoxy-biphenyl-4-yl)-propionic acid 5463-[(5-Hydroxy-1-phenyl-1H-pyrazole-3-carbonyl)-amino]-3-(4- 0.532645methoxy-2-trifluoromethyl-phenyl)-propionic acid 5473-(2-Fluoro-5-methoxy-phenyl)-3-[(5-hydroxy-1-phenyl-1H- 1.388069pyrazole-3-carbonyl)-amino]-propionic acid 5483-[(5-Hydroxy-1-phenyl-1H-pyrazole-3-carbonyl)-amino]-3-(2- 7.759644methoxy-5-trifluoromethyl-phenyl)-propionic acid 5493-[(5-Hydroxy-1-phenyl-1H-pyrazole-3-carbonyl)-amino]-3-(4- 13.812548methoxy-biphenyl-3-yl)-propionic acid 5503-{[1-(2-Fluoro-phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- 0.635486amino}-3-(4-[1,2,4]triazol-1-yl-phenyl)-propionic acid 5513-{[1-(2-Fluoro-phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- 0.352071amino}-3-(3-methoxy-biphenyl-4-yl)-propionic acid 5523-{[1-(2-Fluoro-phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- 0.323441amino}-3-(4-methoxy-2-trifluoromethyl-phenyl)-propionic acid 5533-(2-Fluoro-5-methoxy-phenyl)-3-{[1-(2-fluoro-phenyl)-5- 0.732366hydroxy-1H-pyrazole-3-carbonyl]-amino}-propionic acid 5543-{[1-(2-Fluoro-phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- 1.843808amino}-3-(2-methoxy-5-trifluoromethyl-phenyl)-propionic acid 5553-(2-Fluoro-4-methyl-phenyl)-3-{[1-(2-fluoro-phenyl)-5-hydroxy- 0.2385781H-pyrazole-3-carbonyl]-amino}-propionic acid 5563-{[1-(2-Fluoro-phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- 8.652812amino}-3-(4-methoxy-biphenyl-3-yl)-propionic acid 5573-{[1-(2-Chloro-phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- 0.839178amino}-3-(4-[1,2,4]triazol-1-yl-phenyl)-propionic acid 5583-{[1-(2-Chloro-phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- 0.699161amino}-3-(3-methoxy-biphenyl-4-yl)-propionic acid 5593-{[1-(2-Chloro-phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- 0.731295amino}-3-(2-fluoro-5-methoxy-phenyl)-propionic acid 5603-{[1-(2-Chloro-phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- 7.623283amino}-3-(2-methoxy-5-trifluoromethyl-phenyl)-propionic acid 5613-{[1-(2-Chloro-phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- 0.265803amino}-3-(2-fluoro-4-methyl-phenyl)-propionic acid 5623-{[1-(2-Chloro-phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- 4.493781amino}-3-(4-methoxy-biphenyl-3-yl)-propionic acid 5633-[(5-Hydroxy-1-phenyl-1H-pyrazole-3-carbonyl)-amino]-3-(4- 1.74027[1,2,4]triazol-1-yl-phenyl)-propionic acid 5643-(2-Fluoro-4-methyl-phenyl)-3-[(5-hydroxy-1-phenyl-1H- 0.458522pyrazole-3-carbonyl)-amino]-propionic acid 5653-[(5-Hydroxy-1-phenyl-1H-pyrazole-3-carbonyl)-amino]-3-(4- 5.022589pyrrolidin-1-yl-phenyl)-propionic acid 5663-{[1-(2-Fluoro-phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- 2.986143amino}-3-(4-pyrrolidin-1-yl-phenyl)-propionic acid 5673-{[1-(2-Chloro-phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- 1.062689amino}-3-(4-methoxy-2-trifluoromethyl-phenyl)-propionic acid 5683-{[1-(2-Chloro-phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]- 2.354354amino}-3-(4-pyrrolidin-1-yl-phenyl)-propionic acid 745(S)-3-{[1-(2-Fluoro-phenyl)-5-((R)-2-hydroxy-3,3-dimethyl- 0.004703butoxy)-1H-pyrazole-3-carbonyl]-amino}-3-o-tolyl-propionic acid 747(S)-3-{[1-(2-Fluoro-phenyl)-5-((R)-2-hydroxy-2,3,3-trimethyl- 0.014724butoxy)-1H-pyrazole-3-carbonyl]-amino}-3-o-tolyl-propionic acid 748(S)-3-{[1-(2-Fluoro-phenyl)-5-((S)-2-hydroxy-2,3,3-trimethyl- 0.002558butoxy)-1H-pyrazole-3-carbonyl]-amino}-3-o-tolyl-propionic acid 753(S)-3-(2,4-Dichloro-phenyl)-3-{[1-(2-fluoro-phenyl)-5-((R)-2- 0.3449hydroxy-3,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}- propionicacid 758 (S)-3-(2-Chloro-phenyl)-3-{[1-(2-fluoro-phenyl)-5-((R)-2-0.01742 hydroxy-2,3,3-trimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic acid 766(S)-3-{[1-(2-Fluoro-phenyl)-5-((S)-2-hydroxy-2,3-dimethyl- 0.000692butoxy)-1H-pyrazole-3-carbonyl]-amino}-3-p-tolyl-propionic acid 768(S)-3-(4-Fluoro-phenyl)-3-{[1-(2-fluoro-phenyl)-5-((R)-2-hydroxy-0.00115 2,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionicacid 771(S)-3-(4-Fluoro-phenyl)-3-{[1-(2-fluoro-phenyl)-5-((R)-2-hydroxy-0.00197 2,3,3-trimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic acid 8033-Cyclohexyl-3-{[1-(2-fluoro-phenyl)-5-((S)-2-hydroxy-2,3- 0.0267dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionic acid 860(S)-3-{[1-(2-Fluoro-phenyl)-5-((R)-2-hydroxy-2,3-dimethyl- 0.0761butoxy)-1H-pyrazole-3-carbonyl]-amino}-3-p-tolyl-propionic acid 870(S)-3-{[1-(2-Fluoro-phenyl)-5-((S)-2-hydroxy-2,3-dimethyl- 0.076butoxy)-1H-pyrazole-3-carbonyl]-amino}-3-o-tolyl-propionic acid

The invention claimed is:
 1. A compound of the formula I, in any of itsstereoisomeric forms or a mixture of stereoisomeric forms in any ratio,or a physiologically acceptable salt thereof, or a physiologicallyacceptable solvate of any of them,

wherein A is chosen from the series consisting of C(R¹) and N; D ischosen from the series consisting of N(R²), O and S; E is chosen fromthe series consisting of C(R³) and N; G is chosen from the seriesconsisting of R⁷¹—O—C(O)—, R⁷²—N(R⁷³)—C(O)—, NC— and tetrazol-5-yl; R¹is chosen from the series consisting of hydrogen, halogen,(C₁-C₆)-alkyl, Ar, HO—, (C₁-C₆)-alkyl-O—, (C₁-C₆)-alkyl-S(O)_(m)— andNC—; R² is chosen from the series consisting of (C₁-C₇)-alkyl,(C₃-C₇)-cycloalkyl-C_(s)H_(2s)— and Ar—C_(s)H_(2s)—, wherein s is aninteger chosen from the series consisting of 0, 1, 2 and 3; R³ is chosenfrom the series consisting of hydrogen, halogen, (C₁-C₆)-alkyl,(C₁-C₆)-alkyl-O—, (C₁-C₆)-alkyl-S(O)_(m)— and NC—; R¹⁰ is chosen fromthe series consisting of R¹¹—O—, R¹²—N(R¹³)—C(O)—O— and Het²—C(O)—O—;R¹¹ is chosen from the series consisting of hydrogen, R¹⁴,(C₃-C₇)-cycloalkyl, Ar and Het³; R¹² and R¹³ are independently of eachother chosen from the series consisting of hydrogen, R¹⁵ and Ar; R¹⁴ is(C₁-C₁₀)-alkyl which is optionally substituted by one or more identicalor different substituents chosen from the series consisting of halogen,HO—, R¹⁶—O—, oxo, (C₃-C₇)-cycloalkyl, Ar, Het¹, Het³, NC—, H₂N—C(O)—,(C₁-C₄)-alkyl-NH—C(O)—, di((C₁-C₄)-alkyl)N—C(O)—, Het¹—C(O)—,(C₁-C₄)-alkyl-C(O)—NH— and (C₁-C₄)-alkyl-S(O)_(m)—; R¹⁵ is (C₁-C₆)-alkylwhich is optionally substituted by one or more identical or differentsubstituents chosen from the series consisting halogen, HO— and(C₁-C₆)-alkyl-O—; R¹⁶ is (C₁-C₆)-alkyl which is optionally substitutedby one or more identical or different substituents chosen from theseries consisting of HO—, (C₁-C₄)-alkyl-O— and NC—; R³⁰ is chosen fromthe series consisting of R³¹, (C₃-C₇)-cycloalkyl, R³²—C_(u)H_(2u)— andHet³—C_(u)H_(2u)—, wherein u is an integer chosen from the seriesconsisting of 0, 1, 2 and 3; R³¹ is (C₁-C₁₀)-alkyl which is optionallysubstituted by one or more identical or different substituents chosenfrom the series consisting of halogen, (C₃-C₇)-cycloalkyl, HO—,(C₁-C₆)-alkyl-O—, (C₁-C₆)-alkyl-S(O)_(m)— and NC—; R³² is chosen fromthe series consisting of phenyl and an aromatic 5-membered or 6-memberedmonocyclic heterocycle which comprises one, two or three identical ordifferent ring heteroatoms chosen from the series consisting ofnitrogen, oxygen and sulfur and is bonded via a ring carbon atom,wherein the phenyl and the heterocycle all are optionally substituted byone or more identical or different substituents chosen from the seriesconsisting of halogen, (C₁-C₆)-alkyl, (C₃-C₇)-cycloalkyl, R³³, HO—,(C₁-C₆)-alkyl-O—, R³³—O—, R³³—(C₁-C₄)-alkyl-O—, —O—CH₂—O—, —O—CF₂—O—,(C₁-C₆)-alkyl-S(O)_(m), H₂N—S(O)₂—, (C₁-C₄)-alkyl-NH—S(O)₂—,di((C₁-C₄)-alkyl)N—S(O)₂—, H₂N—, (C₁-C₆)-alkyl-NH—, di((C₁-C₆)-alkyl)N—,Het¹, (C₁-C₄)-alkyl-C(O)—NH—, Ar—C(O)—NH—, (C₁-C₄)-alkyl-S(O)₂—NH— andNC—; R³³ is chosen from the series consisting of phenyl and an aromatic5-membered or 6-membered monocyclic heterocycle which comprises one, twoor three identical or different ring heteroatoms chosen from the seriesconsisting of nitrogen, oxygen and sulfur and is bonded via a ringcarbon atom, wherein the phenyl and the heterocycle all are optionallysubstituted by one or more identical or different substituents chosenfrom the series consisting of halogen, (C₁-C₆)-alkyl,(C₃-C₇)-cycloalkyl, HO—, (C₁-C₆)-alkyl-O—, (C₁-C₆)-alkyl-S(O)_(m)—,H₂N—S(O)₂—, (C₁-C₄)-alkyl-NH—S(O)₂—, di((C₁-C₄)-alkyl)N—S(O)₂— and NC—;R⁴⁰ is chosen from the series consisting of hydrogen and (C₁-C₄)-alkyl;or R³⁰ and R⁴⁰ together are (CH₂)_(x) which is optionally substituted byone or more identical or different (C₁-C₄)-alkyl substituents, wherein xis an integer chosen from the series consisting of 2, 3, 4 and 5; R⁵⁰ ischosen from the series consisting of hydrogen, (C₁-C₆)-alkyl, HO— and(C₁-C₆)-alkyl-O—; R⁶⁰ is chosen from the series consisting of hydrogenand (C₁-C₆)-alkyl; or R⁵⁰ and R⁶⁰ together are (CH₂)_(y) which isoptionally substituted by one or more identical or different(C₁-C₄)-alkyl substituents, wherein y is an integer chosen from theseries consisting of 2, 3, 4 and 5; R⁷¹ is chosen from the seriesconsisting of hydrogen and (C₁-C₈)-alkyl which is optionally substitutedby one or more identical or different substituents chosen from theseries consisting (C₁-C₆)-alkyl-O— and (C₁-C₆)-alkyl-C(O)—O—; R⁷² ischosen from the series consisting of hydrogen, (C₁-C₆)-alkyl,(C₃-C₆)-cycloalkyl, —CH₂—(CH₂)_(b)—(C₃-C₆)-cycloalkyl, Het⁴ and—(CH₂)_(b)—Het⁴, where alkyl or cycloalkyl is optionally substituted byone or more identical or different substituents chosen from the seriesconsisting of halogen, HO—, HOOC—, (C₁-C₆)-alkyl-O— and(C₁-C₆)-alkyl-C(O)—O—, NC—, N((C₁-C₄)-alkyl)₂ and b is 0, 1 or 2; R⁷³ ischosen from the series consisting of hydrogen, (C₁-C₆)-alkyl; or R⁷² andR⁷³ together with the nitrogen atom to which they are bonded form asaturated 4-membered to 7-membered monocyclic heterocycle, which containoptionally one further ring heteroatom chosen from the series consistingof nitrogen, oxygen and sulfur, which is optionally substituted by oneor more identical or different substituents chosen from the seriesconsisting of halogen, (C₁-C₄)-alkyl, HO— and (C₁-C₄)-alkyl-O—; Ar,independently of each other group Ar, is chosen from the seriesconsisting of phenyl and an aromatic 5-membered or 6-membered monocyclicheterocycle which comprises one, two or three identical or differentring heteroatoms chosen from the series consisting of nitrogen, oxygenand sulfur and is bonded via a ring carbon atom, wherein the phenyl andthe heterocycle all are optionally substituted by one or more identicalor different substituents chosen from the series consisting of halogen,(C₁-C₆)-alkyl, (C₁-C₆)-alkyl-O—, —O—CH₂—O—, —O—CF₂—O—,(C₁-C₆)-alkyl-S(O)_(m)—, H₂N—S(O)₂— and NC—; Het¹, independently of eachother group Het¹, is a saturated or unsaturated 4-membered to 8-memberedmonocyclic heterocycle which comprises a ring nitrogen atom via whichHet¹ is bonded and optionally one or two identical or different furtherring heteroatoms chosen from the series consisting of nitrogen, oxygenand sulfur, which is optionally substituted by one or more identical ordifferent substituents chosen from the series consisting of halogen,(C₁-C₄)-alkyl, HO—, (C₁-C₄)-alkyl-O—, oxo and NC—; Het² is a saturated4-membered to 7-membered monocyclic heterocycle which comprises a ringnitrogen atom via which Het² is bonded and optionally one further ringheteroatom chosen from the series consisting of nitrogen, oxygen andsulfur, which is optionally substituted by one or more identical ordifferent substituents chosen from the series consisting of halogen,(C₁-C₄)-alkyl, HO— and (C₁-C₄)alkyl-O—; Het³, independently of eachother group Het³, is a saturated 4-membered to 7-membered monocyclicheterocycle which comprises one or two identical or different ringheteroatoms chosen from the series consisting of nitrogen, oxygen andsulfur and is bonded via a ring carbon atom, which is optionallysubstituted by one or more identical or different substituents chosenfrom the series consisting of fluorine, (C₁-C₄)-alkyl and oxo; Het⁴,independently of each other group Het⁴, is a saturated or unsaturated4-membered to 8-membered monocyclic heterocycle which comprises one tofour ring heteroatoms chosen from the series consisting of nitrogen,oxygen and sulfur which is optionally substituted by one or moreidentical or different substituents chosen from the series consisting ofhalogen, (C₁-C₄)-alkyl, HO—, (C₁-C₄)-alkyl-O—, oxo and NC—; m,independently of each other number m, is an integer chosen from theseries consisting of 0, 1 and 2; wherein all cycloalkyl groups,independently of each other, are optionally substituted by one or moreidentical or different substituents chosen from the series consisting offluorine and (C₁-C₄)-alkyl; wherein all alkyl, C_(s)H_(2s), C_(u)H_(2u), (CH₂)_(x) and (CH₂)_(y) groups, independently of each other, andindependently of any other substituents, are optionally substituted byone or more fluorine substituents.
 2. The compound of the formula I, inany of its stereoisomeric forms or a mixture of stereoisomeric forms inany ratio, or a physiologically acceptable salt thereof, or aphysiologically acceptable solvate of any of them, as claimed in claim1, wherein E is N.
 3. The compound of the formula I, in any of itsstereoisomeric forms or a mixture of stereoisomeric forms in any ratio,or a physiologically acceptable salt thereof, or a physiologicallyacceptable solvate of any of them, as claimed in claim 1, wherein D isN(R²).
 4. The compound of the formula I, in any of its stereoisomericforms or a mixture of stereoisomeric forms in any ratio, or aphysiologically acceptable salt thereof, or a physiologically acceptablesolvate of any of them, as claimed in claim 1, wherein A is chosen fromthe series consisting of C(R¹) and N; D is N(R²); E is N; R¹ is chosenfrom the series consisting of hydrogen, halogen and (C₁-C₄)-alkyl; R² isAr—C_(s)H_(2s)—, wherein s is an integer chosen from the seriesconsisting of 0, 1 and
 2. 5. The compound of the formula I, in any ofits stereoisomeric forms or a mixture of stereoisomeric forms in anyratio, or a physiologically acceptable salt thereof, or aphysiologically acceptable solvate of any of them, as claimed in claim1, wherein R¹⁰ is R¹¹—O—.
 6. The compound of the formula I, in any ofits stereoisomeric forms or a mixture of stereoisomeric forms in anyratio, or a physiologically acceptable salt thereof, or aphysiologically acceptable solvate of any of them, as claimed in claim1, wherein R³⁰ is R³²—C_(u)H_(2u)— wherein u is an integer chosen fromthe series consisting of 0 and
 1. 7. The compound of the formula I, inany of its stereoisomeric forms or a mixture of stereoisomeric forms inany ratio, or a physiologically acceptable salt thereof, or aphysiologically acceptable solvate of any of them, as claimed in claim1, wherein G is chosen from the series consisting of R⁷¹—O—C(O)— andR⁷²—N(R⁷³)—C(O)—; R³⁰ is R³²—C_(u)H_(2u)—, wherein u is an integerchosen from the series consisting of 0 and 1; R³² is chosen from theseries consisting of phenyl and an aromatic 6-membered monocyclicheterocycle which comprises one or two nitrogen atoms as ringheteroatoms, wherein the phenyl and the heterocycle all are optionallysubstituted by one, two or three identical or different substituentschosen from the series consisting of halogen, (C₁-C₆)-alkyl,(C₃-C₇)-cycloalkyl, R³³, (C₁-C₆)-alkyl-O—, R³³—O—, R³³—(C₁-C₄)-alkyl-O—,—O—CH₂—O—, —O—CF₂—O—, (C₁-C₆)-alkyl-S(O)_(m)—, (C₁-C₆)-alkyl-NH—,di((C₁-C₆)-alkyl)N—, Het¹ and NC—; R³³ is chosen from the seriesconsisting of phenyl and pyridinyl which all are optionally substitutedby one, two or three identical or different substituents chosen from theseries consisting of halogen, (C₁-C₄)-alkyl, (C₁-C₄)-alkyl-O—,(C₁-C₄)-alkyl-S(O)_(m)— and NC—; R⁴⁰ is hydrogen; R⁵⁰ is hydrogen; R⁶⁰is hydrogen.
 8. The compound of the formula I, in any of itsstereoisomeric forms or a mixture of stereoisomeric forms in any ratio,or a physiologically acceptable salt thereof, or a physiologicallyacceptable solvate of any of them, as claimed in claim 1, wherein A ischosen from the series consisting of C(R¹) and N; D is N(R²); E ischosen from the series consisting of C(R³) and N; G is chosen from theseries consisting of R⁷¹—O—C(O)— and R⁷²—N(R⁷³)—C(O)—; R¹ is chosen fromthe series consisting of hydrogen, halogen, (C₁-C₆)-alkyl, HO— and(C₁-C₆)-alkyl-O—; R² is chosen from the series consisting of(C₁-C₇)-alkyl, (C₃-C₇)-cycloalkyl-C_(s)H_(2s)— and Ar—C_(s)H_(2s)—,wherein s is an integer chosen from the series consisting of 0, 1, 2 and3; R³ is chosen from the series consisting of hydrogen, halogen,(C₁-C₆)-alkyl and (C₁-C₆)-alkyl-O—; R¹⁰ is chosen from the seriesconsisting of R¹¹—O—, R¹²—N(R¹³)—C(O)—O— and Het²—C(O)—O—; R¹¹ is chosenfrom the series consisting of hydrogen, R¹⁴, (C₃-C₇)-cycloalkyl andHet³; R¹² and R¹³ are independently of each other chosen from the seriesconsisting of hydrogen, R¹⁵ and Ar; R¹⁴ is (C₁-C₁₀)-alkyl which isoptionally substituted by one or more identical or differentsubstituents chosen from the series consisting of halogen, HO—, R¹⁶—O—,oxo, (C₃-C₇)-cycloalkyl, Ar, Het¹, Het³, NC—, H₂N—C(O)—,(C₁-C₄)-alkyl-NH—C(O)—, di((C₁-C₄)-alkyl)N—C(O)— and Het¹—C(O)—; R¹⁵ is(C₁-C₆)-alkyl; R¹⁶ is (C₁-C₆)-alkyl which is optionally substituted byone or more identical or different substituents chosen from the seriesconsisting of HO— and (C₁-C₄)-alkyl-O—; R³⁰ is chosen from the seriesconsisting of (C₃-C₇)-cycloalkyl, R³²—C_(u)H_(2u)— andHet³—C_(u)H_(2u)—, wherein u is an integer chosen from the seriesconsisting of 0, 1, 2 and 3; R³² is chosen from the series consisting ofphenyl and an aromatic 6-membered monocyclic heterocycle which comprisesone or two nitrogen atoms as ring heteroatoms, wherein the phenyl andthe heterocycle all are optionally substituted by one or more identicalor different substituents chosen from the series consisting of halogen,(C₁-C₆)-alkyl, (C₃-C₇)-cycloalkyl, R³³, HO—, (C₁-C₆)-alkyl-O—, R³³—O—,R³³—(C₁-C₄)-alkyl-O—, —O—CH₂—O—, —O—CF₂—O—, (C₁-C₆)-alkyl-S(O)_(m)—,di((C₁-C₄)-alkyl)N—S(O)₂—, H₂N—, di((C₁-C₆)-alkyl)N—, Het¹,(C₁-C₄)-alkyl-C(O)—NH—, Ar—C(O)—NH— and NC—; R³³ is chosen from theseries consisting of phenyl and an aromatic 6-membered monocyclicheterocycle which comprises one or two nitrogen atoms as ringheteroatoms, wherein the phenyl and the heterocycle all are optionallysubstituted by one or more identical or different substituents chosenfrom the series consisting of halogen, (C₁-C₆)-alkyl,(C₃-C₇)-cycloalkyl, HO—, (C₁-C₆)-alkyl-O—, (C₁-C₆)-alkyl-S(O)_(m)—,H₂N—S(O)₂—, di((C₁-C₄)-alkyl)N—S(O)₂— and NC—; R⁴⁰ is hydrogen; R⁵⁰ ischosen from the series consisting of hydrogen and HO—; R⁶⁰ is hydrogen;R⁷¹ is chosen from the series consisting of hydrogen and (C₁-C₈)-alkylwhich is optionally substituted by one or more identical or differentsubstituents chosen from the series consisting (C₁-C₆)-alkyl-O— and(C₁-C₆)-alkyl-C(O)—O—; R⁷² and R⁷³ are independently of each otherchosen from the series consisting of hydrogen and (C₁-C₄)-alkyl; Ar,independently of each other group Ar, is chosen from the seriesconsisting of phenyl and an aromatic 5-membered or 6-membered monocyclicheterocycle which comprises one, two or three identical or differentring heteroatoms chosen from the series consisting of nitrogen, oxygenand sulfur and is bonded via a ring carbon atom, wherein the phenyl andthe heterocycle all are optionally substituted by one or more identicalor different substituents chosen from the series consisting of halogen,(C₁-C₆)-alkyl, (C₁-C₆)-alkyl-O—, —O—CH₂—O—, —O—CF₂—O—,(C₁-C₆)-alkyl-S(O)_(m)—and NC—; Het¹, independently of each other groupHet¹, is a saturated or unsaturated 4-membered to 8-membered monocyclicheterocycle which comprises a ring nitrogen atom via which Het¹ isbonded and optionally one or two identical or different further ringheteroatoms chosen from the series consisting of nitrogen, oxygen andsulfur, which is optionally substituted by one or more identical ordifferent substituents chosen from the series consisting of halogen,(C₁-C₄)-alkyl, HO—, (C₁-C₄)-alkyl-O—, oxo and NC—; Het² is a saturated4-membered to 7-membered monocyclic heterocycle which comprises a ringnitrogen atom via which Het² is bonded and optionally one further ringheteroatom chosen from the series consisting of nitrogen, oxygen andsulfur, which is optionally substituted by one or more identical ordifferent substituents chosen from the series consisting of halogen,(C₁-C₄)-alkyl, HO— and (C₁-C₄)-alkyl-O—; Het³, independently of eachother group Het³, is a saturated 4-membered to 7-membered monocyclicheterocycle which comprises one or two identical or different ringheteroatoms chosen from the series consisting of nitrogen, oxygen andsulfur and is bonded via a ring carbon atom, which is optionallysubstituted by one or more identical or different substituents chosenfrom the series consisting of fluorine, (C₁-C₄)-alkyl and oxo; m,independently of each other number m, is an integer chosen from theseries consisting of 0, 1 and 2; wherein all cycloalkyl groups,independently of each other, are optionally substituted by one or moreidentical or different substituents chosen from the series consisting offluorine and (C₁-C₄)-alkyl; p1 wherein all alkyl, C_(s)H_(2s),C_(u)H_(2u), (CH₂)_(x) and (CH₂)_(y) groups, independently of eachother, and independently of any other substituents, are optionallysubstituted by one or more fluorine substituents.
 9. The compound of theformula I, in any of its stereoisomeric forms or a mixture ofstereoisomeric forms in any ratio, or a physiologically acceptable saltthereof, or a physiologically acceptable solvate of any of them, asclaimed in claim 1, wherein A is C(R¹); D is N(R²); E is N; G is chosenfrom the series consisting of R⁷¹—O—C(O)— and R⁷²—N(R⁷³)—C(O)—; R¹ ischosen from the series consisting of hydrogen, halogen and(C₁-C₄)-alkyl; R² is Ar—C_(s)H_(2s)—, wherein s is 0; R¹⁰ is R¹¹—O—; R¹¹is chosen from the series consisting of hydrogen and R¹⁴; R¹⁴ is(C₁-C₁₀)-alkyl which is optionally substituted by one, two or threeidentical or different substituents chosen from the series consisting ofHO—, R¹⁶—O—, oxo, (C₃-C₇)-cycloalkyl, Ar, Het¹, di((C₁-C₄)-alkyl)N— andHet¹—C(O)—; R¹⁶ is (C₁-C₆)-alkyl which is optionally substituted by oneor two identical or different substituents chosen from the seriesconsisting of HO— and (C₁-C₄)-alkyl-O—; R³⁰ is R³²—C_(u)H_(2u)—, whereinu is an integer chosen from the series consisting of 0 and 1; R³² ischosen from the series consisting of phenyl and an aromatic 6-memberedmonocyclic heterocycle which comprises one or two nitrogen atoms as ringheteroatoms, wherein the phenyl and the heterocycle all are optionallysubstituted by one, two or three identical or different substituentschosen from the series consisting of halogen, (C₁-C₆)-alkyl,(C₃-C₇)-cycloalkyl, R³³, (C₁-C₆)-alkyl-O—, R³³—O—, R³³—(C₁-C₄)-alkyl-O—,—O—CH₂—O—, —O—CF₂—O—, (C₁-C₆)-alkyl-S(O)_(m)—, di((C₁-C₆)-alkyl)N—, Het¹and NC—; R³³ is chosen from the series consisting of phenyl andpyridinyl which all are optionally substituted by one, two or threeidentical or different substituents chosen from the series consisting ofhalogen, (C₁-C₄)-alkyl, (C₁-C₄)-alkyl-O—, (C₁-C₄)-alkyl-S(O)_(m)— andNC—; R⁴⁰ is hydrogen; R⁵⁰ is hydrogen; R⁶⁰ is hydrogen; R⁷¹ is chosenfrom the series consisting of hydrogen and (C₁-C₈-alkyl which isoptionally substituted by one substituent chosen from the seriesconsisting (C₁-C₆)-alkyl-O— and (C₁-C₆)-alkyl-C(O)—O—; R⁷² and R⁷³ areindependently of each other chosen from the series consisting ofhydrogen and (C₁-C₂)-alkyl; Ar is chosen from the series consisting ofphenyl and an aromatic 6-membered heterocycle which comprises one or twonitrogen atoms as ring heteroatoms, wherein the phenyl and theheterocycle are all optionally substituted by one, two or threeidentical or different substituents chosen from the series consisting ofhalogen, (C₁-C₆)-alkyl, (C₁-C₆)-alkyl-O—, (C₁-C₆)-alkyl-S(O)_(m)— andNC—; Het¹, independently of each other group Het¹, is a saturated orunsaturated 4-membered to 6-membered monocyclic heterocycle whichcomprises a ring nitrogen atom via which Het¹ is bonded and optionallyone further ring heteroatom chosen from the series consisting ofnitrogen, oxygen and sulfur, which is optionally substituted by one, twoor three identical or different substituents chosen from the seriesconsisting of fluorine, (C₁-C₄)-alkyl, HO— and oxo; m, independently ofeach other number m, is an integer chosen from the series consisting of0, 1 and 2; wherein all cycloalkyl groups, independently of each other,are optionally substituted by one or more identical or differentsubstituents chosen from the series consisting of fluorine and(C₁-C₄)-alkyl; wherein all alkyl, C_(s)H_(2s) and C_(u)H_(2u) groups,independently of each other, and independently of any othersubstituents, are optionally substituted by one or more fluorinesubstituents.
 10. The compound of the formula I, or a physiologicallyacceptable salt thereof, or a physiologically acceptable solvate of anyof them, as claimed in claim 1, chosen from3-[(5-Hydroxy-1-phenyl-1H-pyrazole-3-carbonyl)-amino]-3-(4-methoxy-phenyl)-propionicacid,3-(3-tert-Butoxy-phenyl)-3-{[1-(2,5-dimethyl-phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]-amino}-propionicacid,(S)-3-{[1-(2-Fluoro-phenyl)-5-methoxy-1H-pyrazole-3-carbonyl]-amino}-3-o-tolyl-propionicacid,3-(3-Fluoro-2-methyl-phenyl)-3-{[1-(4-fluoro-phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]-amino}-propionicacid,3-(2-Chloro-5-fluoro-phenyl)-3-{[1-(4-fluoro-phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]-amino}-propionicacid,(S)-3-[(5-Methoxy-1-phenyl-1H-pyrazole-3-carbonyl)-amino]-3-o-tolyl-propionicacid,3-[(5-Hydroxy-1-phenyl-1H-pyrazole-3-carbonyl)-amino]-3-(2-methoxy-5-trifluoromethyl-phenyl)-propionicacid,3-(2-Fluoro-4-methyl-phenyl)-3-[(5-hydroxy-1-phenyl-1H-pyrazole-3-carbonyl)-amino]-propionicacid,3-{[1-(2-Chloro-phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]-amino}-3-(2′-fluoro-biphenyl-4-yl)-propionicacid,3-[(5-Methoxy-1-phenyl-1H-pyrazole-3-carbonyl)-amino]-3-(4-pyridin-2-yl-phenyl)-propionicacid,3-{[1-(2-Fluoro-phenyl)-5-hydroxy-1H-pyrazole-3-carbonyl]-amino}-3-(4-methanesulfonyl-phenyl)-propionicacid,(S)-3-{[5-Hydroxy-1-(2-methanesulfonyl-phenyl)-1H)-pyrazole-3-carbonyl]-amino}-3-o-tolyl-propionicacid,3-{[1-(2-Fluoro-phenyl)-5-methoxy-1H-pyrazole-3-carbonyl]-amino}-3-(4-methoxy-2-methyl-phenyl)-propionicacid,(S)-3-{[1-(2-Fluoro-phenyl)-5-methoxy-1H-pyrazole-3-carbonyl]-amino}-3-(2-trifluoromethyl-phenyl)-propionicacid,3-(2,3-Dimethyl-phenyl)-3-{[1-(2-fluoro-phenyl)-5-methoxy-1H-pyrazole-3-carbonyl]-amino}-propionicacid,3-{[5-Cyclopropylmethoxy-1-(2-fluoro-phenyl)-1H-pyrazole-3-carbonyl]-amino}-3-(3-fluoro-2-methyl-phenyl)-propionicacid,(S)-3-{[5-Cyclopropylmethoxy-1-(2-fluoro-phenyl)-1H-pyrazole-3-carbonyl]-amino}-3-m-tolyl-propionicacid,(S)-3-{[1-(2-Fluoro-phenyl)-5-((R)-2-hydroxy-3,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-3-o-tolyl-propionicacid,(S)-3-{[1-(2-fluoro-phenyl)-5-((S)-2-hydroxy-3,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-3-o-tolyl-propionicacid,(S)-3-{[5-(3,3-Dimethyl-2-oxo-butoxy)-1-(2-fluoro-phenyl)-1H-pyrazole-3-carbonyl]-amino}-3-o-tolyl-propionicacid,(S)-3-(2,4-Dichloro-phenyl)-3-{[1-(2-fluoro-phenyl)-5-(2-hydroxy-2-methyl-propoxy)-1H-pyrazole-3-carbonyl]-amino}-propionicacid,(S)-3-{[5-(2-Cyclopropyl-2-hydroxy-propoxy)-1-(2-fluoro-phenyl)-1H-pyrazole-3-carbonyl]-amino}-3-o-tolyl-propionicacid,(S)-3-{[1-(2-Fluoro-phenyl)-5-((R)-2-hydroxy-2,3,3-trimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-3-o-tolyl-propionicacid,(S)-3-{[1-(2-Fluoro-phenyl)-5-((S)-2-hydroxy-2,3,3-trimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-3-o-tolyl-propionicacid,(S)-3-(2-Chloro-phenyl)-3-{[1-(2-fluoro-phenyl)-5-((R)-2-hydroxy-2,3,3-trimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionicacid,(S)-3-(2-Chloro-phenyl)-3-{[1-(2-fluoro-phenyl)-5-((S)-2-hydroxy-2,3,3-trimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionicacid,(S)-3-(2,4-Dichloro-phenyl)-3-{[5-(2-ethyl-2-hydroxy-butoxy)-1-(2-fluoro-phenyl)-1H-pyrazole-3-carbonyl]-amino}-propionicacid,(S)-3-{[1-(2-Fluoro-phenyl)-5-((R)-2-hydroxy-2,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-3-o-tolyl-propionicacid,(S)-3-{[1-(2-Fluoro-phenyl)-5-((S)-2-hydroxy-2,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-3-o-tolyl-propionicacid,(S)-3-(2-Chloro-phenyl)-3-{[1-(2-fluoro-phenyl)-5-((R)-2-hydroxy-3,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionicacid,(S)-3-(2-Chloro-phenyl)-3-{[1-(2-fluoro-phenyl)-5-((S)-2-hydroxy-3,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-propionicacid,(S)-3-{[1-(2-Fluoro-phenyl)-5-((R)-2-hydroxy-2,3,3-trimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-3-p-tolyl-propionicacid,(S)-3-{[1-(2-Fluoro-phenyl)-5-((S)-2-hydroxy-2,3,3-trimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-3-p-tolyl-propionicacid,(S)-3-{[5-((R)-2-Hydroxy-3,3-dimethyl-butoxy)-1-phenyl-1H-pyrazole-3-carbonyl]-amino}-3-phenyl-propionicacid,(S)-3-{[5-((S)-2-Hydroxy-3,3-dimethyl-butoxy)-1-phenyl-1H-pyrazole-3-carbonyl]-amino}-3-phenyl-propionicacid,(S)-3-{[1-(2-Chloro-phenyl)-5-((R)-2-hydroxy-3,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-3-phenyl-propionicacid, and(S)-3-{[1-(2-Chloro-phenyl)-5-((S)-2-hydroxy-3,3-dimethyl-butoxy)-1H-pyrazole-3-carbonyl]-amino}-3-phenyl-propionicacid.
 11. A process for the preparation of a compound of the formula Ior a physiologically acceptable salt thereof or a physiologicallysolvate of any of them as claimed in claim 1, comprising reacting acompound of the formula II with a compound of the formula III,

wherein the groups A, D, E, G, R¹⁰, R³⁰, R⁴⁰, R⁵⁰ and R⁶⁰ in thecompounds of the formulae II and III are defined as in the compounds ofthe formula I and additionally functional groups can be present inprotected form or in the form of a precursor group, and the group J inthe compound of the formula II is HO—, (C₁-C₄)-alkyl-O— or halogen. 12.A pharmaceutical composition comprising the compound of claim 1 or aphysiologically acceptable salt thereof or a physiologically acceptablesolvate thereof.
 13. The pharmaceutical composition according to claim12, further comprising a pharmaceutically acceptable carrier.
 14. Amethod of treating heart failure, congestive heart failure,cardiomyopathy, myocardial infarction, left ventricular dysfunction,cardiac hypertrophy, valvular heart diseases, hypertension,atherosclerosis, peripheral arterial occlusive disease, restenosis,vascular permeability disorders, treatment of edema, thrombosis,rheumatoid arthritis, osteoarthritis, renal failure, cystic fibrosis,chronic bronchitis, chronic obstructive pulmonary disease, asthma,immunological diseases, diabetic complications, fibrotic diseases, pain,ischemia or reperfusion damage or neurodegenerative diseases, or forcardioprotection or renoprotection or as a diuretic (stand-alonetreatment or in combination with established diuretics) in a patient inneed thereof comprising administering to said patient a therapeuticallyeffective amount of the pharmaceutical composition of claim 12.